AA Genotype Group Research Articles

Low-Density Lipoprotein Receptor Apolipoprotein B Gene Polymorphism in Kurdish Patients With Severe Hypercholesterolemia.

Background Polymorphisms in the low-density lipoprotein receptor (LDLR) and apolipoprotein B 100 (APOB-100) genes have been linked to severe hypercholesterolemia in several populations. This study investigated the frequency of LDLR-Ava II and APOB-Xba I polymorphisms among Kurdish patients with severe hypercholesterolemia. Methodology We investigated LDLR-Ava II and APOB-Xba I gene polymorphisms in Kurdish patients attending the Duhok Specialized Laboratory Center in Duhok, Kurdistan Region, Iraq. We included a total of 80 subjects in this study, of which 40 (20 males and 20 females) had severe hypercholesterolemia, and 40 apparently healthy volunteers (21 males and 19 females) had normocholesterolemia, served as a control group. We used the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique to determine the polymorphisms of the LDLR-Ava II and APOB-Xba I genes. Results In those with severe hypercholesterolemia, the observed allele frequencies were AA LDLR-Ava II polymorphism (eight, 20%) followed by TT APOB-Xba I polymorphisms (six, 15%), whereas these frequencies were five (12.5%) and one (2.5%) in those with normocholesterolemia, respectively. The AA genotype group had considerably higher cholesterol and LDL-C levels compared with the GG genotype group. A similar pattern was observed when comparing the TT and CC genotype groups. Conclusions Our results showed a high frequency of AA LDLR-Ava II polymorphism in conjunction with TT APOB-Xba I polymorphism which may be strongly associated with hypercholesterolemia in the Kurdish population.

Impact of MAOA Gene Polymorphism on the Efficacy of Antidepressant Treatment and Craving Severity for Betel Quid Use Disorder.

Betel quid (BQ) use disorder (BUD) is prevalent in many Asian countries, impacting approximately 600 million people. We conducted a randomized clinical trial to analyze the impact of MAOA genetic variations on the severity of BQ craving. This was measured using DSM-5 criteria and the Yale-Brown Obsessive-Compulsive Scale modified for betel quid use (Y-BOCS-BQ). Participants were grouped according to the severity of BUD and MAOA gene single-nucleotide polymorphism (SNP) rs5953210 genotypes. The Y-BOCS-BQ scores were assessed at baseline (week 0) and during follow-up at weeks 2, 4, 6, and 8. The AA genotype group showed significantly greater reductions in Y-BOCS-BQ at weeks 2 (p = 0.0194), 4 (p = 0.0078), 6 (p = 0.0277), and 8 (p = 0.0376) compared to the GG genotype group. Additionally, within the antidepressant group, the AA genotype showed significant reductions in the Y-BOCS-BQ scores at weeks 2 (p = 0.0313), 4 (p = 0.0134), 6 (p = 0.0061), and 8 (p = 0.0241) compared to the GG genotype. The statistical analysis revealed a significant interaction between the treatment and placebo groups based on MAOA genotypes, with the AA genotype in the treatment group exhibiting a more pronounced decrease in Y-BOCS-BQ score (p interaction <0.05) at week 6. Our study highlights the importance of considering genetic factors when developing personalized treatment plans for BUD.

The MACROD2 rs6110695 A>G Polymorphism and the Metabolites Indoleacrylic Acid and Butyrylcarnitine Potentially Have Clinical Relevance to WBC Count Prediction.

Our previous study suggested that the Mono-ADP ribosylhydrolase 2 (MACROD2) rs6110695 A>G polymorphism is significantly associated with white blood cell (WBC) count in the Korean population. The present study aimed to evaluate the clinical relevance of the MACROD2 rs6110695 A>G polymorphism for predicting WBC count by utilizing plasma metabolites and a single-nucleotide polymorphism (SNP). Two groups were characterized by MACROD2 rs6110695 A>G SNP genotypes among 139 healthy subjects based on the genetic information provided in our previous work: rs6110695 AA genotype group (n = 129) and rs6110695 AG genotype group (n = 10). Plasma global metabolic profiling was performed using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). To estimate the predictive abilities of WBC count models using the rs6110695 genotype and/or significant differential metabolites, multiple linear regression analysis and receiver operating characteristic (ROC) curve analysis were conducted. The AG genotype had greater WBC-to-apolipoprotein (apo) A-I ratios; counts of WBCs, lymphocytes, monocytes, and granulocytes; monocyte-to-lymphocyte ratio (MLR); and monocyte-to-platelet ratio (MPR) than the AA genotype. In terms of metabolic profile, indoleacetic acid, and butyrylcarnitine levels were considerably distinct between the two groups, and these metabolites were considered to be meaningful prognostic variables for the rs6110695 genotype. Finally, ROC curve analysis demonstrated that the model containing the rs6110695 genotype and the two main metabolites was reliable. The present study revealed that individuals carrying the rs6110695 AG genotype with high plasma indoleacrylic acid and butyrylcarnitine levels might have elevated WBC counts. The rs6110695 genotype and the concentrations of indoleacrylic acid and butyrylcarnitine could contribute to reducing the risk of chronic diseases in the future.

Association between uncoupling protein 1-3826 A/G polymorphism and the effects of anaerobic exercises on serum oxidative stress

ObjectivesAerobic exercise promotes uncoupling protein-1 (UCP-1) induced white adipose tissue browning by increasing serum nitric oxide (NO), irisin and interleukin-6 (IL-6). However, oxidative stress (OS) occurring during anaerobic exercise downregulates UCP-1. Moreover, UCP-1-3826 A/G polymorphism (UCP1P) is associated with weight gain due to impaired thermogenesis which may be due to UCP1P induced modification in OS. Therefore, our purpose was to investigate the role of UCP1P on the effects of acute maximal exercise (AME) and chronic anaerobic exercise (CAT) on serum OS, UCP-1, NO, irisin and IL-6 levels. Equipments and methodsSport group (SG, n=43) was formed of anaerobic athletes, while control group (CG, n=43) comprised physically inactive men. Postprandial blood was taken from SG and CG before and after AME to determine serum UCP-1, irisin, IL-6, NO, and oxidative stress index (OSI=total oxidant/antioxidant status [TOS/TAS] ratio). To investigate the effects of CAT on serum parameters, SG and CG's results were compared. UCP1P was determined by restriction fragment length polymorphism analysis. ResultsAME significantly increased all parameters in SG and CG (P<0.05). However, CAT increased only OSI and IL-6 (P<0.05), decreased UCP-1 and TAS and did not affect TOS, NO and irisin. OSI of GG homozygous athletes were significantly higher than other genotype groups (P<0.05). Although significant negative correlations were found between UCP-1 and OS markers in GG and AA genotype groups before AME, significant positive correlations were found between UCP-1 and TAS in AA genotype group after AME. GG homozygous athletes may be more prone to higher OS. Decrease in UCP-1 due to CAT may be affected by GG genotype group's genetic disposition for OS.

Killer Cell Immunoglobulin-like Receptor Genotypes and Reproductive Outcomes in a Group of Infertile Women: A Romanian Study.

A growing body of evidence suggests that endometrial immune disorders may be responsible for endometrial dysfunctions that can lead to gynecological and obstetrical pathology. The aim of this study was to explore the potential relationship between different killer cell immunoglobulin-like receptor (KIR) genotypes and reproductive outcomes. We conducted a prospective cohort study that included 104 infertile patients undergoing an in vitro fertilization procedure. All participants underwent clinical and ultrasound examination, genetic evaluation (KIR genotyping), endometrial washing fluid sampling for cytokine determination, endometrial tissue sampling for histologic assessment and hysteroscopic evaluation. Our analysis showed statistically significant lower levels of uterine cytokines TNF-α (p = 0.001) and IL-1beta (p = 0.000) in the KIR AA genotype group as compared to KIR AB and BB among study participants with chronic endometritis. The study results suggest that the KIR AA genotype population subgroups may be more susceptible to developing endometrial disorders such as chronic endometritis. The changes in the behavior of NK cells seem to be subtle and expressed as an altered regulatory pattern.

SLC2A9 rs1014290 Polymorphism is Associated with Prediabetes and Type 2 Diabetes.

To investigate the association of the A/G rs1014290 polymorphism in SLC2A9 with type 2 diabetes (T2DM) and prediabetes mellitus (pre-DM). Patients and Methods. We enrolled 1058 patients who attended the Hebei General Hospital, Shijiazhuang, Hebei Province, China. The patients underwent general testing and oral glucose tolerance tests and were divided into three groups: 352 patients newly diagnosed with T2DM, 358 patients with pre-DM, and 348 healthy controls. The single nucleotide polymorphism (SNP) was detected by ligase detection reactions. The χ 2 test, one-way ANOVA, and binary logistic regression analysis were used to analyze the results. In the T2DM group, the GG genotype frequency at the rs1014290 locus was significantly lower (14.8%) than it was in the healthy controls. Furthermore, the GG genotype group was associated with a reduced risk of T2DM in unadjusted and confounder-adjusted models compared with the risk in the AA genotype group. The G allele in the SLC2A9 rs1014290 locus decreased susceptibility to T2DM. In the pre-DM group, the GG and AG genotype groups had no significant correlation with the risk of pre-DM in any of the models. In the T2DM group, the uric acid level was significantly lower in the GG genotype group. In the T2DM and pre-DM groups, the HOMA-β levels were significantly higher in the GA (P < 0.001) and GG (P < 0.001) genotype groups than it was in the AA genotype group, and HOMA-IR was significantly lower in the GA (P < 0.001) and GG (P < 0.001) genotype groups than it was in the AA genotype group. The A/G (rs1014290) SNP in SLC2A9 is closely related to the occurrence and development of diabetes.

Association of the MACROD2 rs6110695 A>G polymorphism with an increasing WBC count in a Korean population.

IntroductionWe aimed to find a novel candidate gene related to the white blood cell (WBC) count in a Korean population. Since WBC count has been reported to have a relation to the risk of chronic diseases according to previous literature, WBC level prediction can be helpful for managing future risk of chronic disease development. In this aspect, a gene newly found in the present study is expected to be utilized as a tool for judging an individual's WBC level.MethodsBased on the 153 study participants' genotype data produced by the Korean Chip. The mono‐adenosine diphosphate ribosylhydrolase 2 (MACROD2) rs6110695 A>G polymorphism had a significant strong association with WBC count, thus, the MACROD2 gene emerged as a novel candidate gene for WBC count. To verify the effects of the single‐nucleotide polymorphisms on WBC count, the participants were grouped according to the rs6110695 AA and AG genotypes.ResultsWBC to apolipoprotein A‐I ratio, WBC count, granulocyte to lymphocyte ratio, monocyte to platelet ratio, and interferon‐γ level were significantly higher in the AG genotype group than in the AA genotype group. Through the receiver operating characteristic curve analysis, the rs6110695 AA and AG genotypes were discriminated by the optimal WBC count cutoff value of 5.450. As expected, the results in the participants having a WBC count over 5.450 were similar to the AG genotype group.ConclusionsWe revealed that the MACROD2 rs6110695 AG genotype has an association with increasing WBC count. Since, as previous literature described, WBC count is one of the main risk factors for chronic diseases, WBC count measurement in individuals with the rs6110695 AG genotype that was found in the present study may help manage future chronic disease risk.

Gender Difference in the Link of MMP-9 Gene Polymorphism to Serum Matrix Metalloproteinase Level in the Determination of Lung Function in South Indian Population

Background and Aim: Matrixins or matrix metalloproteinases (MMP) belong to metzincin superfamily and they are involved in many physiological functions like extracellular matrix remodeling, angiogenesis, bone growth and neuritic growth. Polymorphisms in MMP-9 gene will result in over expression of matrix metalloproteinases leading to excessive extracellular matrix degradation, which cannot be overcome by the anti-proteinases. One such polymorphism of MMP-9 is Gln279Arg. Degradation of pulmonary matrix can lead to chronic obstructive pulmonary disease. Studies in the past have demonstrated female preponderance in incidence of COPD among smokers. Methods: This was a cross sectional study conducted among healthy volunteers of age group 18 to 45 years. Pulmonary function tests of the subjects were recorded using computerised spirometry (SPIROLAB III). Frequency of Gln279Arg polymorphism was estimated by RT-PCR. Serum MMP-9 were estimated by Enzyme linked Immunosorbent Assay. Results: MMP-9 levels were found to be elevated in AA genotype group in females. Conclusion: The females with AA genotype, have increased MMP-9 levels and so they may be more prone for COPD if they are exposed to the environmental risk factors.

Evidence of Association between MTRR and TNF-α Gene Polymorphisms and Oral Health-Related Quality of Life in Children with Anterior Open Bite.

To assess the impact of AOB on OHRQoL in children and to evaluate whether MTR (rs1805087), MTRR (rs1801394), TGFβ1 (rs1800469) and TNF-α (rs1799964, rs1799724 and rs1800629) genes are potential biomarkers for OHRQoL in children with AOB. A cross-sectional study was performed with 173 children aged between 2-6 years. The Brazilian version of Early Childhood Oral Health Impact Scale (ECOHIS) was applied. Genetic polymorphisms were analyzed using real-time PCR. Mann-Whitney U-test and Chi-square were used. The overall mean ECOHIS scores were 5.49 (SD= 5.72) and 3.45 (SD = 4.49) (p < 0.01) in the AOB and control groups, respectively. Children with the CC genotype of TNF-α (rs1799724) had a significantly higher psychological QoL level. The MTRR AA genotype group showed a lower QoL level in the child subscale (p = 0.006), function (p = 0.017), and psychological (p = 0.006) domains. There was no significant difference between OHRQoL and the genetic polymorphisms in MTR and TGFβ1. Genetic polymorphisms in TNF-α and MTRR are associated with the impact on the OHRQoL in children with AOB.

Tumor Necrosis Factor-α Gene Polymorphism is Associated with Short- and Long-Term Kidney Allograft Outcomes.

IntroductionKidney transplantation has excellent short-term results with current immunosuppression regimes, but long-term outcomes have barely improved over the past two decades. Hence, there is a need for new therapeutic options to increase long-term survival of kidney grafts. Drug development for kidney transplantation has slowly plateaued, limiting progress while making drug repurposing an attractive alternative. We, therefore, investigated the impact of tumor necrosis factor-alpha (TNF-α) gene (TNF) polymorphisms on kidney graft survival after transplantation.MethodsWe performed a prospective cohort study to assess the association of TNF polymorphisms (rs1800629 G>A and rs3093662 A>G) with primary non-function and death-censored kidney allograft survival in 1271 kidney transplant pairs from the University Medical Center Groningen in The Netherlands.ResultsThe G-allele of the TNF rs3093662 polymorphism in donor kidneys was associated with a higher risk of immediate graft loss (odds ratio: 2.05; 95%-CI: 1.06–3.97; P = 0.032). Furthermore, the G-allele of this TNF rs3093662 polymorphism in the donor was also associated with worse 5-year, 10-year, and 15-year death-censored kidney graft survival (P < 0.05). The cumulative incidence of graft loss was 15.9% in the reference AA-genotype group and 25.2% in the AG/GG-genotype group, respectively. In multivariable analysis, the association between the TNF rs3093662 polymorphism in the donor and 15-year death-censored kidney graft survival remained significant (hazard ratio: 1.51; 95%-CI: 1.05–2.19, P = 0.028).DiscussionIn conclusion, kidney allografts possessing a high-producing TNF polymorphism have a greater risk of immediate and late graft loss. Our study adds to a growing body of literature indicating the potential of TNF-α blockade in improving kidney transplantation outcomes.

P-117 Pre-selected for an award: Bioinformatic analysis of NRF2 in the study of association of NRF2 variant and male infertility related to smoking status

Abstract Study question Could Nrf2 polymorphism (-617C&amp;gt;A; rs6721961) and oxidative stress (OS)-induced changes of signature seminal plasma (SP) miRNAs related to Nrf2 provide possible biomarkers of male infertility? Summary answer -617C&amp;gt;A SNP is associated with infertility through sperm OS DNA damage and miR-582-5p and miR-20a-5p, differentially represented between spermatozoa of smokers-non-smokers, might regulate Nrf2/ARE axis. What is known already As an extrinsic factor causing OS, smoking decreases male infertility by causing sperm membrane damage and DNA fragmentation. Expression of proteins related to the antioxidant defense system and phase 2 detoxifying enzymes controlled mainly by Nrf2/ARE pathway components is vital in managing OS-induced DNA damage. miRNAs, which multiple of are produced abundantly in male germ cells throughout spermatogenesis, have been detected in SP and contribute to multiple biological processes related to male reproductive events. miRNA-expression alterations may be induced in response to OS and without involving DNA sequence changes, miRNAs can provide additional mechanism of regulating the Nrf2 gene expression. Study design, size, duration Wild-type (WT) and SNP (-617) alleles in the Nrf2 gene were studied in 100 infertile cases and 100 controls and their associations with seminal parameters in relation to smoking status were assessed. In infertile cases, sperm DNA damage level was determined and compared among Nrf2 genotypes. Interactions between differentially expressed miRNAs (DEMIs) in response to smoking and Nrf2/ARE pathway components were visualized on a miRNA-mRNA regulatory network using CluePedia (v1.5.7) plugin of Cytoscape software (v3.8.2). Participants/materials, setting, methods Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was utilized to genotype the Nrf2 SNP (-617). DNA damages were analyzed by Comet assay. DEMIs were identified by a comprehensive bioinformatics analysis using the miRNA expression dataset GSE44134 downloaded from the GEO database. Predicted targets of DEMIs in smokers were identified by mirDIP portal. Known interactions between Nrf2 and its first neighbors were visualized after selecting STRING-actions, miRTarBase and miRecords validated miRNA source files from CluePedia panel. Main results and the role of chance There was significant difference for Nrf2 polymorphism between fertile and infertile males. The A allele was detected more frequently in the patient group; (P = 0.001). The frequencies of the C and A alleles of the Nrf2 were 62% and 38% in patients, and 78% and 44% in control group. The AA genotype was higher in the infertiles; 14% vs. 3% (P = 0.001). In smokers, sperm quality decreased significantly in AA genotype. The risk of DNA damage was highest with 224.58 AU in the AA genotype group, whereas it is the lowest with 164.56 AU in those carrying the CC genotype (P &amp;lt; 0.005). 21 differentially expressed miRNAs (including 7 downregulated and 14 upregulated in smokers) were identified. Among the upregulated DEMIs, miR-582-5p, miR-20a-5p, miR-573, miR-186-5p, miR-499a-5p were found to target the Nrf2 mRNA, suggesting their usage as biomarkers capable of indicating the antioxidant ability of the male reproductive system. The interrelations between Nrf2/Nrf2 direct interactors and DEMIs revealed the regulatory role of hsa-miR-20a-5p in SQSTM1/p62-Keap1-Nrf2 axis linked to selective autophagy. hsa-miR-582-5p was found to regulate the JNK/Jun/caspase-3 pathway, previously shown to be activated in response to OS, in which JUN can activate or suppress the Nrf2 expression. Limitations, reasons for caution Small number of cases while evaluating the effect of smoking weakens our ability to generalize the results. Including other coexisting factors and larger patient groups carrying other functional variants of Nrf2 as well as confirming the results at the protein level would further strengthen the results of the study. Wider implications of the findings This study is the first to report -617C&amp;gt;A polymorphism in the Nrf2 gene in the Turkish population and such a SNP may cause impaired fertility in men, especially in smokers, through oxidative metabolism. Considering these data may be valuable in determining risk groups. Trial registration number N/A

P–117 Bioinformatic analysis of NRF2 in the study of association of NRF2 variant and male infertility related to smoking status

Abstract Study question Could Nrf2 polymorphism (–617C&amp;gt;A; rs6721961) and oxidative stress (OS)-induced changes of signature seminal plasma (SP) miRNAs related to Nrf2 provide possible biomarkers of male infertility? Summary answer –617C&amp;gt;A SNP is associated with infertility through sperm OS DNA damage and miR–582–5p and miR–20a–5p, differentially represented between spermatozoa of smokers-non-smokers, might regulate Nrf2/ARE axis. What is known already As an extrinsic factor causing OS, smoking decreases male infertility by causing sperm membrane damage and DNA fragmentation. Expression of proteins related to the antioxidant defense system and phase 2 detoxifying enzymes controlled mainly by Nrf2/ARE pathway components is vital in managing OS-induced DNA damage. miRNAs, which multiple of are produced abundantly in male germ cells throughout spermatogenesis, have been detected in SP and contribute to multiple biological processes related to male reproductive events. miRNA-expression alterations may be induced in response to OS and without involving DNA sequence changes, miRNAs can provide additional mechanism of regulating the Nrf2 gene expression. Study design, size, duration Wild-type (WT) and SNP (–617) alleles in the Nrf2 gene were studied in 100 infertile cases and 100 controls and their associations with seminal parameters in relation to smoking status were assessed. In infertile cases, sperm DNA damage level was determined and compared among Nrf2 genotypes. Interactions between differentially expressed miRNAs (DEMIs) in response to smoking and Nrf2/ARE pathway components were visualized on a miRNA-mRNA regulatory network using CluePedia (v1.5.7) plugin of Cytoscape software (v3.8.2). Participants/materials, setting, methods Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was utilized to genotype the Nrf2 SNP (–617). DNA damages were analyzed by Comet assay. DEMIs were identified by a comprehensive bioinformatics analysis using the miRNA expression dataset GSE44134 downloaded from the GEO database. Predicted targets of DEMIs in smokers were identified by mirDIP portal. Known interactions between Nrf2 and its first neighbors were visualized after selecting STRING-actions, miRTarBase and miRecords validated miRNA source files from CluePedia panel. Main results and the role of chance There was significant difference for Nrf2 polymorphism between fertile and infertile males. The A allele was detected more frequently in the patient group; (P = 0.001). The frequencies of the C and A alleles of the Nrf2 were 62% and 38% in patients, and 78% and 44% in control group. The AA genotype was higher in the infertiles; 14% vs. 3% (P = 0.001). In smokers, sperm quality decreased significantly in AA genotype. The risk of DNA damage was highest with 224.58 AU in the AA genotype group, whereas it is the lowest with 164.56 AU in those carrying the CC genotype (P &amp;lt; 0.005). 21 differentially expressed miRNAs (including 7 downregulated and 14 upregulated in smokers) were identified. Among the upregulated DEMIs, miR–582–5p, miR–20a–5p, miR–573, miR–186–5p, miR–499a–5p were found to target the Nrf2 mRNA, suggesting their usage as biomarkers capable of indicating the antioxidant ability of the male reproductive system. The interrelations between Nrf2/Nrf2 direct interactors and DEMIs revealed the regulatory role of hsa-miR–20a–5p in SQSTM1/p62-Keap1-Nrf2 axis linked to selective autophagy. hsa-miR–582–5p was found to regulate the JNK/Jun/caspase–3 pathway, previously shown to be activated in response to OS, in which JUN can activate or suppress the Nrf2 expression. Limitations, reasons for caution Small number of cases while evaluating the effect of smoking weakens our ability to generalize the results. Including other coexisting factors and larger patient groups carrying other functional variants of Nrf2 as well as confirming the results at the protein level would further strengthen the results of the study. Wider implications of the findings: This study is the first to report –617C&amp;gt;A polymorphism in the Nrf2 gene in the Turkish population and such a SNP may cause impaired fertility in men, especially in smokers, through oxidative metabolism. Considering these data may be valuable in determining risk groups. Trial registration number N/A

ESR1 gene polymorphism (rs827421) as a potential genetic marker for constitutional delay of growth and puberty in Egyptian adolescents

Constitutional delay of growth and puberty (CDGP) is a variant of normal pubertal timing and progress. It is the most common form of delayed puberty in both genders. The genetic director of CDGP is ill-understood despite the positive family history result noted in those patients. The current study aimed at assessing the role of estrogen receptor 1 (ESR1) gene variant (rs827421) in Egyptian adolescents with CDGP. A cross-sectional study with follow-up part was carried out on 6760 children aged 4 to15 years. The study focused generally on children aged 13–15 years in order to evaluate the prevalence of delayed puberty in relation to all ages in general and to their peers in specific. Assessment of serum TSH, FSH, and LH was conducted on all participants, along with the measurement of serum-free testosterone for males and estradiol for females. Genotyping of ESR1 (rs827421) was done to all subjects through the use of TaqMan discrimination assay by real-time PCR. ESR1 (rs827421) GG genotype and G allele were significantly dominant among CDGP adolescents in comparison with controls (OR = 25.67 and 6.90). As regards follow-up of testicular size, AA genotype was significantly associated with increased size in the right and left testis compared to other genotypes (P = 0.021 and 0.006, respectively). Moreover, AA genotype showed significantly higher Tanner stage in both males and females in comparison with other genotypes. Serum estradiol level was significantly higher in AA genotype group than other genotypes groups. ESR1 gene polymorphism can be considered a potential genetic marker for CDGP in both sexes in a sample of Egyptian adolescents.

Variation of uncoupling protein 2 (–866G/A), dietary fat intake and blood pressure: an Indonesian Nutrigenetic Cohort

Abstract Background/Introduction The uncoupling protein 2 (UCP2) is recently being recognized as an important molecule involved in the development of cardiovascular diseases such as vascular dysfunction, atherosclerosis, and hypertension. It was previously reported that the UPC2 –866 G/A gene variation was associated with obesity and hypertension. Purpose The objective of this study was to investigate the association between UCP2 –866 G/A gene variation on changes in blood pressure after 2 years of follow up. Additionally, we investigate the interaction between UCP2 –866G/A and dietary fat on changes in blood pressure. Methods This was a cohort study conducted in 503 men and women without chronic diseases in the city of Yogyakarta, Indonesia. Bodyweight, systolic (SBP) and diastolic blood pressure (DBP) were measured at baseline and after 2 years while the dietary intake was recorded once within 2 years period using a semi-quantitative food frequency questionnaire. Subjects were divided based on UCP2 gene variations: GG genotype and GA+AA genotypes. Results There was no difference in blood pressure at baseline between UCP2 genotypes (SBP AA+GA vs. GG: 130.5±26.3 vs. 127.2±24.9 mmHg, p=0.178; DBP AA+GA vs. GG: 80.9±16.1 vs. 78.9±13.8 mmHg, p=0.171). After 2 years, a total of 310 individuals were followed and measured (AA+GA n=197; GG n=113). In all subjects, there was a significant reduction in SBP (from 130.6±26.3 to 126.4±22.8 mmHg, p&amp;lt;0.001) and increment in DBP (from 80.9±15.5 to 82.2±13.7 mmHg, p=0.013). Subjects in GA + AA genotype group had a greater reduction in SBP (−5.3±15.4 vs. −1.5±18.0 mmHg, p=0.018) and lesser increment in DBP (0.7±10.6 vs. 2.7±12.2 mmHg, p=0.045). In this study, we showed that sex and age were not associated with changes in blood pressure (all p&amp;gt;0.05) but changes in body weight were positively correlated with SBP (r=0.219, p&amp;lt;0.001) and DBP (r=0.227, p&amp;lt;0.001). In all subjects, energy, protein, and carbohydrate intake were not correlated with changes in SBP and DBP (all p&amp;gt;0.05). By contrast, total fat intake (B=0.137, p=0.017), saturated fat (B=0.123, p=0.032) and MUFA (B=0.142, p=0.014) were positively correlated with increased SBP while PUFA, trans fat, and cholesterol were not correlated with SBP. There was no correlation between dietary intake and changes in DBP. Among subjects with GA+AA genotype, total fat, saturated fat and MUFA were positively correlated with changes in SBP (all p&amp;lt;0.05) but these correlations were not seen among subjects with GG genotype (all p&amp;gt;0.05). Conclusion We concluded that UCP2 –866G/A gene variation was associated with changes in blood pressure and those who have an A allele were more protected towards increased blood pressure. Total fat, saturated fat, and MUFA were positively correlated with blood pressure and those with A allele were more responsive to the hypertensive effect of dietary fat. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Universitas Gadjah Mada

Study the Effects of Pit-1 polymorphism on some blood Parameters in dairy cow in Karbala governorate

the aim of this study was to investigate the effect of Pit-1 polymorphism on the some blood parameters in dairy local Iraqi cattle, blood samples were collected from (120) healthy dairy cow breeds aged between (4-6 years), in peak stage (40-120) days of lactation, during period of time beginning from September 2017 till January 2018, in the northeast of rural areas in Karbala province. Amplification Refractory Mutation System (ARMS-PCR) techniques was used to detect Pit-1 polymorphism and to classified the genotyping in to three groups; wild group AA, recessive group BB and heterozygosity group AB.The frequencies of genotypes were recorded as 0.06 for AA, 0.70 for AB and 0.24 for BB on the other handthe frequencies of allele were recorded as 0.41 for Pit-1(A) and 0.59 – Pit-1(B).The current study showed no significant decrease (p, >0.05) in the RBC, Hb&MCHC in AB&BB genotype groups compare with AAgenotype group, also the PCV % was no significant difference in all groups. The conclusion our study showed that not found effects of pit 1 polymorphism on the some blood parameter in dairy cow.

Association of the GATA3 rs3824662A allele with clinical outcomes in adult patients with adult B-ALL.

7023 Background: Inherited GATA3 variants (rs3824662) have been described in higher frequency in both adults and children with Ph-like acute lymphoblastic leukemia (Ph-like ALL) (Perez-Andreu, Nat Genetics 2013; Jain, ASH 2017). The clinical outcomes of Ph-like ALL are well known, and as we have previously described, it as a high-risk subtype of ALL in both children and adults (Roberts, NEJM 2014; Roberts, JCO 2017; Jain, Blood 2017). However, the clinical outcomes of ALL patients with different germline variants of GATA3 that are commonly seen in Ph-like ALL is unknown. Methods: Of the newly diagnosed patients treated at MD Anderson Cancer Center (MDACC) with B-ALL, we performed analyses for the GATA3 rs3824662 variant in 85 patients (42 Ph-like ALL, 43 non-Ph-like ALL). Testing for Ph-like ALL, CRLF2 rearrangement, and GATA3 genotypes was performed as previously described (Jain, ASH 2017). Results: Of the 85 patients, the rs3824662 AA genotype was identified in 22 patients, the AC genotype in 33 patients, and the CC genotype in 29 patients. There was a trend towards increased frequency of Hispanic heritage in the AA genotype (86%) vs AC genotype (61%), vs the CC genotype (31%). Additionally, amongst patients with the AA genotype, 91% had the Ph-like ALL vs 45% of the AC genotype vs 10% of the CC genotype. The median white blood count at diagnosis was 52.1 x 109/L in the AA genotype group, 20 x 109/L in the AC genotype group, and 5.9 x 109/L in the CC genotype group. The 5 year event-free-survival (EFS) of the CC group was 55% vs 36% of the AC group vs 14% of the AA group. The EFS between the 3 genotypic groups was statistically significant with a p value of 0.018. The 5 year overall survival (OS) of the CC group was 64% vs 42% of the AC group vs 14% of the AA group. Conclusions: We observed significant differences in the EFS between patients with 0, 1, 2 copies of this genetic polymorphism in the GATA3 gene. The role of genomic AA GATA3 variant on the biology of ALL and understanding of the downstream mechanisms needs to be determined. [Table: see text]

Lanosterol Synthase Genetic Variants, Endogenous Ouabain, and Both Acute and Chronic Kidney Injury

Studies of humans and animals have suggested that endogenous ouabain (EO) and related genes are mediators of acute (AKI) and chronic kidney injury. We sought to examine the relationship among EO levels, genetic variants in lanosterol synthase (LSS; an enzyme that catalyzes synthesis of cholesterol, a precursor of EO), and both AKI and chronic kidney injury. 2 prospective observational cohort studies and a cross-sectional study of kidney tissue. (1) A prospective cohort study of patients undergoing cardiovascular surgery, (2) measurement of EO concentration in kidney tissue removed because of an adjacent tumor, and (3) a prospective cohort study of patients with newly diagnosed essential hypertension. Missense variant in LSS (A instead of C allele at rs2254524), which leads to a valine to leucine substitution at amino acid642. Development of postoperative AKI in the cardiovascular surgery cohort, EO concentration in kidney tissue, and estimated glomerular filtration rate (eGFR) reductions in the essential hypertension cohort. Logistic regression for analysis of postoperative AKI, analysis of variance for EO concentration in kidney tissue, and generalized linear models for changes in eGFR over time. AKI incidence following cardiovascular surgery was greater among those with the LSS rs2254524 AA genotype (30.7%) than in those with the CC genotype (17.4%; P=0.001). LSS rs2254524 AA kidneys had higher EO concentrations than CC kidneys (2.14±0.29 vs 1.25±0.08ng/g; P<0.001). In the longitudinal study of patients with essential hypertension (median follow-up, 4 years; range, 1-15 years), eGFR decline was greater among the LSS rs2254524 AA genotype group (-4.39±1.18mL/min/1.73m2 per year) than in the AC or CC genotype groups (-1.07±0.55 and-2.00±0.45mL/min/1.73m2 per year respectively; P= 0.03). These associations do not necessarily represent causal relationships; LSS rs2254524 variants may have effects on other steroid hormones. These findings support the potential value of LSS rs2254524 genotype-based risk stratification to identify patients at high risk for AKI before cardiovascular surgery, as well as predict accelerated eGFR in the setting of hypertension. These findings also suggest that LSS may in part drive EO-mediated kidney damage. EO may represent a new potential therapeutic target for the prevention of AKI and slowing of kidney damage in the setting of hypertension.

Plasma stearoyl-CoA desaturase activity indices and bile acid concentrations after a low-fat meal: association with a genetic variant in the FTO gene.

PurposeDietary macronutrient composition, stearoyl-CoA desaturase (SCD) activity indices, and primary bile acid (BA) concentrations are among the factors that have been associated with lipid metabolism and contributed to obesity. We investigated the association between the polymorphic expression of the fat mass and obesity-associated (FTO) gene and its relationship with SCD activity indices and primary BA concentrations after a low-fat meal.Subjects and methodsBlood plasma samples were collected from 56 young (20–36 years) healthy subjects with different rs9939609 FTO genotypes. Fasting and post-meal (2 hours after a low-fat breakfast) blood samples were collected on the subsequent morning for the analysis of DNA methylation, SCD activity indices (product-to-precursor fatty acid ratios; 16:1n-7/16:0 and 18:1n-9/18:0), and chenodeoxycholic acid (CDCA) and cholic acid (CA) concentrations. Expression of lipogenic genes was investigated post-meal to assess the relationship between the CDCA and CA concentrations and mRNA levels of lipogenic genes.ResultsThe FTO AA (obesity risk) genotype group (n=18) had higher (P<0.05) post-meal SCD-16 activity index than the FTO TT (wild type) genotype group (n=26). In both the FTO TT (n=16) and AA (n=8) genotype groups, the post-meal concentrations of CDCA and CA were lower (P<0.05) compared with the fasted state. No difference in BA concentrations between the FTO TT and AA genotype groups in both meal states was observed. After adjusting for the body mass index, the highest 50% post-meal concentrations of CA were inversely (P=0.010) correlated with the level of mRNA SCD expression.ConclusionFTO AA carriers may be at a higher risk for obesity through higher SCD activity in a low-fat diet environment. This effect may be partly pronounced by very low CA concentrations.

Cholesteryl ester transfer protein gene variations and macronutrient intakes interaction in relation to metabolic syndrome: Tehran lipid and glucose study.

Objective(s):There are controversial results regarding the effect of the interaction of CETP polymorphisms with dietary fats on the lipid profiles. The aim of this study was to examine the effect of CETP polymorphisms (rs5882 and rs3764261) and macronutrient intakes interaction in relation to metabolic syndrome (MetS) or its components.Materials and Methods:In this nested case-control study, subjects were selected from among participants of the Tehran Lipid and Glucose Study. Cases (n=441) were individually matched with two controls (844 non-MetS subjects). DNA samples were genotyped with HumanOmniExpress-24-v1-0 bead chips, including 649,932 SNP loci.Results:The mean ages at baseline were 38.1±10 and 37.0±10 years in women and 36.2±11 and 36.3±11 years in men, respectively in cases and controls. We did not find significant gene-diet interactions between rs5882 and dietary macronutrient intakes in relation to MetS risk. The risk of low HDL-C was lower in the first quartile of MUFA and total fat intake in G allele carriers, compared to AA genotype group. The risk of high BP appeared to increase significantly in higher quartiles of trans-fatty acid intakes (>1.81% of total energy intake) in G allele carriers compared with the AA genotype group. No significant interactions were found between rs3764261 and macronutrient intakes in association with MetS or its components.Conclusion:Our findings demonstrate that dietary fats modify the association of rs5882 and risk of low HDL-C and high blood pressure.

Analysis of variants at LGALS3 single nucleotide polymorphism loci in skull base chordoma.

Although LGALS3 has been widely studied, the genotypes of the LGALS3 single nucleotide polymorphism (SNP) loci in skull base chordoma (SBC) have been not well defined. The aim of the current study was to analyze two LGALS3 SNP genotypes in patients with SBC. A total of 48 patients with SBC who underwent surgical treatment in Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University (Beijing, China) and 66 healthy participants were included in the present study. A total of two SNPs (LGALS3+191 C>A and LGALS3 +292 A>C) were selected for sequencing analysis of amplified target fragments from DNA that was extracted from blood samples. The clinical features of the patients were recorded, follow-up was conducted and statistical analysis was performed with SPSS 20.0. There were no differences in age and sex between the patients and control group. In addition, there were no significant differences in the distribution of genotypes (P=0.662) and allelic frequencies (P=0.638) at LGALS3+191 C>A between the two groups. However, significant difference was observed in the allelic distributions at LGALS3 +292 A>C between them (P=0.016), and allele A was associated with the occurrence of SBC. The distribution of the genotypes at LGALS3 +292 A>C was not significantly different in the additive model (CC vs. AC vs. AA, P=0.083) but was significantly different in the dominant model (CC+AC vs. AA, P=0.043). In the Kaplan-Meier analysis, there were no significant differences in the overall survival and progression analysis between different genotypes at LGALS3 +191 C>A (P=0.168 and P=0.120) in patients with SBC. There was no significant difference in overall survival was observed between the genotypes at +292 A>C (P=0.595). However, the progression-free survival (PFS) time of the CC+AC genotype group was longer compared with the AA genotype group (P<0.001). In the univariate and multivariate analysis of tumor progression, PFS was shorter in the AA genotype group compared with the CC+AC genotype group (P<0.001). The allele A and AA genotype at LGALS3 +292 A>C were observed to be associated with a higher risk of SBC, and the AA genotype at +292 A>C was associated with a shorter PFS time.