CG Genotype Research Articles

Evaluation of the effect of MTNR1B rs10830963 gene variant on the therapeutic efficacy of nateglinide in treating type 2 diabetes among Chinese Han patients

Genetic polymorphisms in the MTNR1B gene is associated with type 2 diabetes mellitus (T2DM); however, there is no evidence about its impact on the therapeutic efficacy of nateglinide. This prospective case–control study was designed to investigate the effect of MTNR1B rs10830963 gene variant on the therapeutic efficacy of nateglinide in treating T2DM. We genotyped untreated T2DM patients (N = 200) and healthy controls (N = 200) using the method of the high resolution of melting curve (HRM). Newly diagnosed T2DM patients (n = 60) with CYP2C9*1 and SLCO1B1 521TT genotypes were enrolled and given oral nateglinide (360 mg/d) for 8 weeks. The outcome was measured by collecting the venous blood samples before and at the 8th week of the treatment. The risk G allelic frequency of MTNR1B rs10830963 was higher in T2DM patients than the healthy subjects (P < 0.05). Post 8-week of treatment, newly diagnosed T2DM patients showed a less reduction in fasting plasma glucose levels and less increase in the carriers of genotype CG + GG at rs10830963 when compared with the CC genotype (P < 0.05). MTNR1B rs10830963 polymorphism was associated with the therapeutic efficacy of nateglinide in T2DM patients. Also, the CC homozygotes had a better effect than G allele carriers.Trial registration Chinese Clinical Trial Register ChiCTR13003536, date of registration: May 14, 2013.

ANKS1A genotype predicts cardiovascular events in patients with familial hypercholesterolemia

The rs17609940 variant of the ANKS1A gene has been associated with coronary artery disease (CAD) risk in genome-wide association studies (GWAS), but no study has yet replicated this association in familial hypercholesterolemia (FH) population. The aim of this study is to validate the association between the rs17609940 genotype and incident major adverse cardiovascular events (MACE) in a cohort of genetically-confirmed FH patients. This association study includes 725 genetically-confirmed FH patients with a median observation period of 50 years (33 805 person-years). MACE were defined as either myocardial infarction (MI), stroke, coronary revascularization, hospital admission for unstable angina and cardiovascular disease (CVD) death. The rs17609940 genotype was imputed with an imputation quality of 0.831 following an exome chip genotyping method (Illumina). The cohort comprised 469 subjects with GG genotype, 218 subjects with CG genotype and 38 subjects with CC genotype. All baseline characteristics were balanced between the three groups. The CC genotype of rs17609940 was associated with a significant lower risk of incident MACE compared to GG and GC carriers in a recessive model (HR 0.30, 95% CI 0.11-0.82, p=0.02). Even after correction for confounding cardiovascular risk factors, the association between the ANKS1A polymorphism and incident MACE remained strongly significant. We demonstrated that the rs17609940 SNP of the ANKS1A gene is associated with the risk of incident MACE in FH subjects. The exact mechanism underlying this association remains to be clarified.

Folate metabolizing gene polymorphisms and genetic vulnerability to preterm birth in Korean women.

The folate metabolism that converts homocysteine to methionine is closely related to the accumulation of homocysteine. Increased homocysteine levels lead to an impaired antithrombotic function of the vascular endothelium and uterine-placental circulation, resulting in abnormal pregnancy outcomes. Previous studies have reported that gene polymorphisms in folate metabolism are associated with the development of preterm birth (PTB) in various populations. we performed a case-control study to evaluate the association between five polymorphisms in folate metabolic genes (MTHFR, MTR, MTRR, TCN2) and PTB. In this study, a total of 254 subjects were analyzed (111 patients with PTB and 143 women at ≥ 38weeks of gestation). Genotype and allele frequency differences between patients and control groups and the Hardy-Weinberg equilibrium were assessed using a Chi-square test. For evaluation indicators, odds ratios (ORs) of 95% confidence intervals (CI) were estimated. In addition, we analyzed the combined genotype frequencies of SNPs of folate-metabolizing genes to measure gene-gene interactions for PTB. Our results showed that the MTR rs1805087 GG (p = 0.031), and TCN2 rs1801198 CG genotype (OR 0.53, 95% CI 0.288-0.980, p = 0.042) were significantly associated with PTB. The MTHFR rs4846049 AA showed a marginal trend toward significance (OR 0.15, 95% CI 0.018-1.205, p = 0.041). In particular, the combined genotypes, including MTHFR rs1537514 CC-MTRR rs1801394 GG, MTHFR rs1537514 CC-TCN2 rs1801198 CG, and MTR rs1805087 AA-TCN2 rs1801198 CG, have significant interactions with PTB (OR 0.49, 95% CI 0.248-0.992, p < 0.05). The polymorphisms of folate metabolic genes may have a genetic association with the development of PTB in Korean women. A larger sample set and functional studies are required to further elucidate our findings.

Analysis of association of socs5 gene polymorphism with allergic bronchial asthma and the level of its control

The objective: to analyze the frequency of genotypes and alleles of the rs6737848 polymorphism of the socs5 gene in patients with allergic bronchial asthma (BA) and to assess the association of this polymorphism with different levels of control over this disease.Subjects and methods. 179 people of the Caucasian race were the subjects of the study, and they all had the confirmed diagnosis of allergic asthma. The diagnosis, severity, and level of disease control were assessed in accordance with the GINA recommendations. The comparison group included apparently healthy individuals (n = 217).Results. The study of rs6737848 of the socs5 gene revealed statistically significant differences in the frequencies of genotypes and alleles in the group of patients with allergic asthma versus the group of healthy individuals. Among patients with allergic asthma, the frequency of the CC genotype and C allele was the highest. Carriers of the CG genotype and G allele prevailed among healthy individuals versus allergic asthma patients. Analysis of frequency distribution of genotypes and alleles of the rs6737848 polymorphism of the socs5 gene showed statistically significant predominance of the CC genotype and C allele in the sample of patients with allergic asthma that was fully or partially controlled.Conclusion. In women, the CC genotype and allele C of the socs5 gene can be considered as a genetic risk factor for the development of allergic asthma and a prognostic marker of controlled and partially controlled course of the disease. The CG genotype and G allele of the socs5 gene have a conditionally protective effect on the development of allergic asthma.

Genetic aspects of primary headaches in Siberia (Russia)

Primary headaches are common neurological problem in the world. Migraine (M) and tension type headache (TTH) are the leaders in the structure of primary headaches in the population; (1) Background: The study of the association of single nucleotide variants (SNVs) of MTHFR (meth-ylenetetrahydrofolate reductase) and HTR2C (5-Hydroxytryptamine Receptor 2C) genes with M and TTH development in the European population in Siberia (Russia); (2) Methods: 192 adults were examined: 82 (42.7%) males and 110 (57.3%) females. Control group: 81 healthy adults, median age 49.5 [36; 59] years; 53 (66.7%) males and 27 (33.3%) females. Headache group consisted of 111 patients with primary headache, median age 54 [45; 64] years, including two subgroups: subgroup 1 (M) of 39 patients; subgroup 2 (TTH) of 72 patients. Carriage of alleles and genotypes rs1801133 and rs1801131 of the MTHFR gene and rs6318 of the HTR2C gene was determined using PCR-RT by TaqMan allelic discrimination technology; (3) Results: A statistically significant association of the carriage of the A allele rs1801133 of the MTHFR gene with the formation of M (p = 0.025) and TTH (p = 0.022), as well as the GA genotype with the development of TTH (p = 0.024) was revealed. Carriage of the G allele and the TG and GG genotypes of the MTHFR gene, associated with a decreased activity of the MTHFR enzyme, does not affect the development of primary headache. A statistically significant association was revealed between the carriage of the heterozygous GC genotype (rs6318) of the HTR2C gene and the formation of M (p = 0.013); (4) Conclusions: Carriage of the A allele (OR 1.77; 95% CI 1.09-2.89) and the GA genotype (OR 2.24; 95% CI 1.17-4.29) rs1801133 of the MTHFR gene is a risk factor for the development of TTH (p &lt;0.05). Carriage of the A allele rs1801133 of the MTHFR gene is a risk factor for the development of M (OR 1.97; 95% CI 1.08-3.57; p &lt;0.05). Carriage of the variant G allele and rs1801131 GT and GG genotypes associated with reduced activity of the MTHFR enzyme does not affect the development of primary headache. In the control group, the prevalence of the T allele associated with normal enzymatic activity was noted (p = 0.024). Carriage of the heterozygous genotype CG SNV rs6318 of the HTR2C gene increases the risk of developing migraine by 3.6 times.

The influence of RS738409 I148M polymorphism of patatin-like phospholipase domain containing 3 gene on the susceptibility of non-alcoholic fatty liver disease

We aimed to elucidate the frequency of polymorphic genotypes and alleles of patatin-like phospholipase domain containing 3 rs738409 polymorphism and its possible associations with non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis in a cohort from Turkey.We enrolled 200 patients diagnosed with NAFLD and genotyped for rs738409 I148M polymorphism by real-time polymerase chain reaction, particularly by melting curve analysis. SPSS analysis software was used for statistical significance. Continuous variable values were expressed as mean ± standard deviation. Significant statistical level was chosen as p = 0.05.Our results demonstrate in a cohort from Turkey that rs738409 C > G polymorphism (I148M) of patatin-like phospholipase domain containing 3 gene is significantly able to affect individuals to have NAFLD in unadjusted regression model.Consistent with the previous studies in other populations, our study group showed a significantly higher risk of having NAFLD in unadjusted regression model but not in the adjusted model indicating that non-genetic factors such as age and sex may be responsible for the association. However, independent studies need to validate our findings with a larger group of NAFLD patients, as well as in different ethnic cohorts.

Relationship between postmenopausal osteoporosis and glucocorticoid receptor gene (NR3C1) polymorphism in a Turkish population

IntroductionGlucocorticoids (GCs) are used in the treatment of numerous diseases, and long-term use of GCs causes bone loss. GC receptor activation decreases Bone Mineral Density (BMD) by inhibiting and stimulating osteoblasts and osteoclasts, respectively. GC receptor gene polymorphisms are also associated with increased susceptibility to GCs. The purpose of this study was to assess the relationship between osteoporosis and Glucocorticoid receptor gene (NR3C1) polymorphism in Turkish population.Material and methodsThe study group consisted of 232 unrelated patients with osteoporosis and 150 unrelated healthy controls. All participants, patients and healthy controls, were of Turkish origin, from the central region of Turkey. Genomic DNA was isolated from whole venous blood samples using a commercial DNA isolation kit. The NR3C1 BclI gene C/G polymorphism was analyzed by polymerase chain reaction.ResultsThe frequencies of CC, CG and GG genotypes in the patients were 34.5%, 48.3%, and 17.2% and in the controls were 48.0%, 42.0%, and 10.0%. A statistically significant difference was observed between patients and controls according to genotype frequencies (p=0.01). C and G allele frequencies of C/G polymorphism were 58.6% and 41.4% in patient group and 69.0% and 31.0% in control group (p=0.005).ConclusionsThe NR3C1 BclI gene C/G polymorphism could be one of the genetic factors causing osteoporosis.

Genetic variations of rs6928 and rs5999521 of ERK2 were found to have correlation with the risk of brain metastasis in patients with lung adenocarcinoma.

BackgroundPatients with lung adenocarcinoma with epidermal growth factor receptor (EGFR) mutations have a high risk of brain metastasis (BM). Mitogen-activated protein kinase (MAPK) is an important mediator of EGFR/c-MET crosstalk, which is involved in development of BM in non-small cell lung cancer. Here, we investigated the association of MAPK genetic variations with the risk of BM in patients with lung adenocarcinoma.MethodsPatients with pathologically confirmed lung adenocarcinoma from two Hospitals (n=120, discovery cohort; n=213, validation cohort) were enrolled. Magnetic resonance imaging (MRI) was employed for BM follow-up after the completion of planned therapy. Single nucleotide polymorphisms (SNPs) of MAPK pathway genes were tested with blood samples.ResultsAfter adjustment for sex, age, staging, smoking status, surgery, and thoracic radiotherapy, extracellular signal-regulated kinase 2 (ERK2) rs6928 and rs5999521 SNPs were found to be associated with increased risk of BM. The rs6928 GG and CG genotypes were associated with 2.033-fold (P=0.033) and 1.910-fold (P=0.012) increases in the risk of developing BM compared with the CC genotype. For rs5999521, the risk of developing BM was increased by 1.993-fold (P=0.037) in patients with the GG genotype and 1.834-fold (P=0.019) in patients with the AG genotype compared with patients with the AA genotype. Furthermore, patients with genotypes of higher risk of BM showed higher EGFR mutation rates and tended to have >1 BM lesions.ConclusionsIn patients with lung adenocarcinoma, ERK2 rs6928 and rs5999521 SNPs contributed to BM risk, particularly in patients with specific genotypes.

Association between MIF gene promoter rs755622 and susceptibility to coronary artery disease and inflammatory cytokines in the Chinese Han population

Macrophage migration inhibitory factor (MIF) is an essential mediator of atherosclerotic plaque progression and instability leading to intracoronary thrombosis, therefore contributing to coronary artery disease (CAD). In this study, we investigated the relationship between MIF gene polymorphism and CAD in Chinese Han population. Three single nucleotide polymorphisms (SNP, rs755622, rs1007888 and rs2096525) of MIF gene were genotyped by TaqMan genotyping assay in 1120 control participants and 1176 CAD patients. Coronary angiography was performed in all CAD patients and Gensini score was used to assess the severity of coronary artery lesions. The plasma levels of MIF and other inflammatory mediators were measured by ELISA. The CAD patients had a higher frequency of CC genotype and C allele of rs755622 compared with that in control subjects (CC genotype: 6.5% vs. 3.9%, P = 0.008, C allele: 24.0% vs. 20.6%, P = 0.005). The rs755622 CC genotype was associated with an increased risk of CAD (OR: 1.804, 95%CI: 1.221–2.664, P = 0.003). CAD patients with a variation of rs755622 CC genotype had significantly higher Gensini score compared with patients with GG or CG genotype (all P < 0.05). In addition, the circulating MIF level was highest in CAD patients carrying rs755622 CC genotype (40.7 ± 4.2 ng/mL) and then followed by GC (37.9 ± 3.4 ng/mL) or GG genotype (36.9 ± 3.7 ng/mL, all P < 0.01). Our study showed an essential relationship between the MIF gene rs755622 variation and CAD in Chinese Han population. Individuals who carrying MIF gene rs755622 CC genotype were more susceptible to CAD and had more severe coronary artery lesion. This variation also had a potential influence in circulating MIF levels.

Sequence Polymorphism in Xenobiotic Metabolising Genes in Iraqi Colorectal Cancer Patients.

Objectives:Colorectal cancer (CRC) is the third most prevalent malignant neoplasm. Genetic variations in the xenobiotic metabolising cytochrome enzymes. Family 1 Subfamily A Member 1 (CYP1A1) and Family 1 Subfamily B Member 1 (CYP1B1) might play a role in cancer pathogenesis and prognosis. The aim of this work is to determine the frequency of Single Nucleotide Polymorphisms (SNPs) in CYP1A1 (rs1048943, Ile462VaI and rs4646903/MSP1) and CYP1B1 (rs1056836, Leu432Val) genes in patients with CRC cancer. It was also an attempt to identify the association between SNPs and CRC and its stage and grade at diagnosis. Methods:This case-control study was conducted in Kirkuk/Iraq, 200 patients with CRC and 200 cancer free control subjects were enrolled. Genomic DNA was extracted from venous blood samples and screened for SNPs using Restriction Fragment Length Polymorphism (RFLP) and confirmed by the direct DNA sequencing. Results:The reference genotype of CYP1A1 gene rs1048943 is AA. Both the AG and GG variants were significantly more frequent in the cancer group and associated with increased risks of CRC and its later stages (stages III and IV) and poor differentiation (p<0.01). The reference genotype of CYP1A1 rs4646903 is TT. The variant genotypes, TC and CC, had no significant association with increased odds of cancer (P>0.05) or with tumour stage or its grade (p>0.05). The GG genotype of CYP1B1 rs1056836 was the reference genotype. The CG and CC variants were not associated with increased risks of CRC (P>0.05) or its stage or grade except the CG genotype which was associated with poor differentiation (OR= 3.4, 95 % CI= 1.8 -6.5, P<0.001). Conclusion:CYP1A1 gene rs1048943 SNPs can represent a potential future marker for CRC risk prediction and prognosis. Further evaluation in large scale studies will provide greater understanding of the effects of other genes SNPs on CRC risk and prognosis.

Genetic Association of CYP1B1 4326 C>G Polymorphism with Disease-Free Survival in TNBC Patients Undergoing TAC Chemotherapy Regimen.

Background:Triple negative breast cancer (TNBC) which is treated with taxane, adriamycin and cyclophosphamide (TAC) chemotherapy regimen show variation in treatment response. CYP1B1 4326 C>G polymorphism has been implicated in contributing to the differences in treatment response in various types of cancers. Aim:The objective of the present study was to investigate whether this polymorphism modulate the risk of disease recurrence in TNBC patients undergoing TAC chemotherapy regimen. Methods:Blood samples of 76 immunohistochemistry confirmed TNBC patients were recruited. The genotyping of CYP1B1 4326 C>G polymorphism was carried out using PCR-RFLP technique. The genotype patterns were categorized into homozygous wildtype, heterozygous and homozygous variant. Kaplan-Meier analysis followed by Cox proportional hazard regression model were performed to evaluate the TNBC patients’ recurrence risk. Results:Out of 76 TNBC patients, 25 (33.0%) showed disease recurrence after one-year evaluation. Kaplan Meier analysis showed that TNBC patients who are carriers of CYP1B1 4326 GG variant genotypes (37.0%) had a significantly lower probability of disease-free rates as compared to TNBC patients who are carriers of CYP1B1 4326 CC/CG genotypes (71.0%). Univariate and multivariate Cox analysis demonstrated that TNBC patients who carried CYP1B1 4326 GG variant genotype had a significantly higher risk of recurrence with HR: 2.50 and HR: 4.18 respectively, even after adjustment as compared to TNBC patients who were carriers of CYP1B1 4326 CC and CG genotypes. Conclusion:Our results demonstrate the potential use of CYP1B1 4325 GG variant genotype as a candidate biomarker in predicting risk of recurrence in TNBC patients undergoing TAC chemotherapy regimen.

MiR-146a and miR-155 polymorphisms in Egyptian patients with Behcet's disease.

The current study was designed to analyze whether polymorphisms of miR-146a and miR-155 are related to Behçet's disease (BD) in the Egyptian population. A total of 96 unrelated BD patients and 100 healthy subjects were genotyped for miR-146a (rs2910164) and miR-155 (rs767649) using real-time polymerase chain reaction. The results showed significant elevation in the frequency of rs2910164 GG and CC genotypes in BD patients compared with controls (adjusted OR = 22.156, 95% CI: 4.728-103.818; p < 0.001 and adjusted OR = 40.358, 95% CI: 8.928-182.440; p < 0.001, respectively). Also, the rs2910164 G allele conferred a higher risk of developing BD (adjusted OR = 3.665, 95% CI: 2.013-6.671; p < 0.001). MiR-146a (rs2910164) polymorphism was a risk factor for susceptibility to BD in dominant, recessive and additive models of inheritance (all p < 0.001), while the miR-155 (rs767649) polymorphism was a risk factor in the recessive model only (p = 0.021). GG and CG genotypes of rs2910164 were associated with higher Behcet's disease current activity index (BDCAI) and ocular involvement compared with CC genotype (p = 0.005 and p = 0.004, respectively). Genotype AT of rs767649 was related to higher BDCAI (p = 0.026) compared with TT and AA genotypes. miR-146a (rs2910164) and miR-155 (rs767649) are likely to play an important role in the Egyptian population in development of BD and also influence disease severity.

Molecular Evaluation of MicroRNA-146 Gene Variability (rs2910164 C> G) and its Association with Increased Susceptibility to Coronary Artery Disease.

Apart from the modifiable risk factors, genetic factors are believed to influence the outcome of Coronary Artery Diseases (CAD). Under the genetic factors, miRNA polymorphisms, namely Hsa-miR-146a-5p (rs2910164) have become an important tool to study the mechanism that underlies the pathogenesis of this disease. Therefore, we investigated the association of miR-146a gene variations with susceptibility of coronary artery diseases. This study was conducted on 100 CAD patients and 117 matched healthy individuals. Genotyping of the Hsa-miR-146a-5p C>G gene variation was performed by using Amplification Refractory Mutation System PCR method (ARMS-PCR). The distribution of Hsa-miR-146a-5p rs2910164 C>G genotypes observed between patients and controls was significantly different (P=0.048). Moreover, the frequency of G allele (fG) was found to be significantly higher among patients than in controls (0.36 vs. 0.25). Our findings showed that the Hsa-miR-146a-5p C>G variant was associated with an increased risk of CAD in codominant inheritance model CC vs. CG genotype (OR = 1.84, 95% CI, 1.02-3.31; p=0.040) and (OR = 3.18, 95% CI, 1.02-9.9; p=0.045) for CC vs. GG genotype in dominant inheritance model. Whereas the G allele significantly increased the risk of coronary artery disease (OR =1,81, 95% CI, 1.18-2.78; p=0.006) compared to C allele. Taken together, these results demonstrated that miR-146a/rs2910164 is associated with susceptibility to coronary artery disease, providing novel insights into the genetic etiology and underlying biology of coronary artery disease. Our findings indicated that Hsa-miR-146a-5p rs2910164 GG genotype and G allele are associated with increased susceptibility to Coronary Artery Disease. A larger sample size can be the key to progress in establishing the genetic co-relation of miRNA gene polymorphisms and cardiovascular diseases.

Associations of MDM2 and MDM4 Polymorphisms with Early-Stage Breast Cancer.

Breast cancer is one of the most common cancers worldwide. Single nucleotide polymorphisms (SNPs) in MDM2 and MDM4 have been associated with various cancers. However, the influence on clinical characteristics of breast cancer has not been sufficiently investigated yet. Thus, this study aimed to investigate the relationship between SNPs in MDM2 (rs2279744, rs937283, rs937282) and MDM4 (rs1380576, rs4245739) and I–II stage breast cancer. For analysis, the genomic DNA was extracted from 100 unrelated women peripheral blood. Polymorphisms were analyzed with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. The study showed that MDM2 rs937283 and rs937282 were significantly associated with estrogen receptor status and human epidermal growth factor receptor 2 (HER2) status. SNPs rs1380576 and rs4245739, located in MDM4, were significantly associated with status of estrogen and progesterone receptors. Our findings suggest that rs937283 AG, rs937282 CG, rs1380576 CC, and rs4245739 AA genotypes were linked to hormonal receptor positive breast cancer and may be useful genetic markers for disease assessment.

Clinical Evaluation of Latrophilin 3 (LPHN3) Gene in Children with Attention Deficit Hyperactivity Disorder (ADHD )

This Disorder (attention deficit hyperactivity disorder) is a neurodevelopmental disorder defined by impairing levels of inattention, disorganization, and/or hyperactivity impulsivity. Inattention and disorganization entail inability to stay on task, seeming not to listen, and losing materials, at levels that are inconsistent with age or developmental level. Hyperactivity-impulsivity entails overactivity, fidgeting, inability to stay seated, intruding into other people's activities, and inability to wait symptoms that are excessive for age or developmental level.Attention-Deficit Hyperactivity Disorder is the most commonly diagnosed psychiatric disorder, occurring in 5-7% of children world wide.This study aimed to evaluate the association between LPHN3 gene and attention deficit hyperactivity disorder . Methods: The subjects were 2 groups; Group (I): included 30 patients with attention deficit hyperactivity disorder . And Group (II): included 30 apparently healthy individuals as a control group. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to determine the genetic association of attention deficit hyperactivity disorder with the LPHN3 gene polymorphis (rs2349039). Results: The attention deficit hyperactivity disorder group included 20 male (66.7%) and 10 females (33.3%), the mean age was 9.8±1.8 years. there was a statistically significant difference in the distribution of genotypes of the LPHN3 rs2349039 polymorphism in the attention deficit hyperactivity disorder and control groups, (p=0.01). In attention deficit hyperactivity disorder group; individuals with CG genotype were 5.8 folds to have attention deficit hyperactivity disorder than CC individuals. Also, those with GG genotype were about Six times more likely to have attention deficit hyperactivity disorder than CC ones.

Association of RANKL and OPG Gene Polymorphism in Arab Women with and without Osteoporosis.

Receptor activator of the nuclear factor-κB ligand (RANKL) and osteoprotegerin genes (OPG) were identified as susceptible loci for postmenopausal osteoporosis (PMO) in various ethnicities, but neither have been studied in an Arabian population. Hence, the current study aimed to fill this gap. A total of 372 postmenopausal women (174 osteoporosis (OP) and 198 control group (CTRs)) were genotyped for four SNPs: rs2277438A/G and rs9533156T/C (RANKL), and rs2073618C/G and rs3102735T/C (OPG). Anthropometrics, bone mineral density, 25(OH)D and several other bone markers were measured. The frequency distribution of the heterozygous CG genotype of rs2073618 (OPG) was lower in the OP (36.8%) than in CTRs (47%) (OR: 0.6, 95% CI: 0.3–0.97; p = 0.041). No differences in the allelic/genotypic frequencies were detected between the two groups for all other studied SNPs. However, the heterozygous TC genotype of rs3102735 (OPG) was associated significantly with lower BMD at the femoral neck in OP subjects (p = 0.04). The homozygous rare CC genotype of rs9533156 (RANKL) was associated with lower 25(OH)D levels in CTRs (p = 0.032). In contrast, heterozygous AG genotype of rs2277438 (RANKL) is associated with lower 25(OH)D in the OP group (p = 0.02). Our results suggest that RANKL SNPs may impact 25(OH)D levels and that OPG SNP rs2073618A/G is a significant genetic risk factor for PMO Saudi Arabian women.

Gene expression pattern analysis using dual-color RT-MLPA and integrative genome-wide association studies of eQTL for tuberculosis suscepitibility

BackgroundWhen infected with Mycobacterium tuberculosis, only a small proportion of the population will develop active TB, and the role of host genetic factors in different TB infection status was not fully understood.MethodsForty-three patients with active tuberculosis and 49 with latent tuberculosis were enrolled in the prospective cohort. Expressing levels of 27 candidate mRNAs, which were previously demonstrated to differentially expressed in latent and active TB, were measured by dual color reverse transcription multiplex ligation dependent probe amplification assay (dcRT-MLPA). Using expression levels of these mRNAs as quantitative traits, associations between expression abundance and genome-wild single nucleotide polymorphisms (SNPs) were calculated. Finally, identified candidate SNPs were further assessed for their associations with TB infection status in a validation cohort with 313 Chinese Han cases.ResultsWe identified 9 differentially expressed mRNAs including il7r, il4, il8, tnfrsf1b, pgm5, ccl19, il2ra, marco and fpr1 in the prospective cohort. Through expression quantitative trait loci mapping, we screened out 8 SNPs associated with these mRNAs. Then, CG genotype of the SNP rs62292160 was finally verified to be significantly associated with higher transcription levels of IL4 in LTBI than in TB patients.ConclusionWe reported that the SNP rs62292160 in Chinese Han population may link to higher expression of il4 in latent tuberculosis. Our findings provided a new genetic variation locus for further exploration of the mechanisms of TB and a possible target for TB genetic susceptibility studies, which might aid the clinical decision to precision treatment of TB.

The effect of polymorphisms (174G> C and 572C> G) on the Interleukin-6 gene in coronary artery disease: a systematic review and meta-analysis

BackgroundCoronary Artery Disease (CAD) is caused by the blockage of the coronary arteries. it is argued that there has an association between the Interleukin-6 gene and the occurrence of atherosclerosis, coronary artery disease, Due to the short half-life and high variability of Interleukin-6 (IL-6), limited studies have been performed on the association of serum levels of interleukin-6 with coronary artery disease. The aim of this study is to investigate the relationship between IL-6 gene polymorphisms and coronary artery disease.MethodsThis study was conducted as a meta-analysis of selected articles with no lower time limit and upto March 2020. Articles related to the subject were obtained by searching several data sources,such as the SID, IranDoc, Scopus, Embase, Web of Science (ISI), PubMed, Science Direct, and Google Scholar databases. The heterogeneity of the studies was assessed using the I2 index in the Comprehensive Meta-Analysis software.ResultsThe GG genotype of the IL-6174 G> C polymorphism with a 0.8 odds ratio tended to reduce the risk of CAD by 20%. The odds ratio of CAD in CG and GG genotypes were found to be 1.16 and 1.48 times respectively, indicating the increasing effect of these two genotypes. In the IL-6-572 C>G polymorphism, CG and GG genotypes increased the risk of CAD by 1.21 and 1.27 times respectively, and the CC genotype tended to reduce the risk of CAD by 15%, considering the odds ratio of 0.85.ConclusionThis study showed a relationship between IL-6174G> C and Interleukin-6 (IL-6) 572 C>G genes and coronary artery disease. Moreover, the protective effects of GG genotype in IL-6 gene 174 G> C and CC genotype in IL-6 gene 572 C>G gene were reported. The study also confirmed that the CG and CC genotypes of the G>C IL-6174 gene have an increasing effect on coronary artery disease. Moreover, CG and GG genotypes in the IL-6 gene 572 C>G increased the risk of developing CAD. It should be noted that the increased risk of developing CAD was limited to meta-analytic studies in reported literatures.

Evaluation of IL1B rs1143634 and IL6 rs1800796 Polymorphisms with Autism Spectrum Disorder in the Turkish Children

ABSTRACT Background Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder caused by genetic, environmental and immunological factors. It is known that neural development processes are affected by immune functions. The aim of this study is to evaluate the relationship between cytokines IL6 and IL1B gene polymorphisms in ASD. Methods DNA isolations were performed in 95 children diagnosed with ASD and 84 unrelated healthy children, single-nucleotide changes in IL6 (rs1800796) and IL1B (rs1143634) genes were determined by using Real-Time PCR (Real-Time Polymerase Chain Reaction) method. Results IL6 rs1800796 polymorphism presented an elevated risk for the development of ASD with CG genotype and dominant model (CG+GG vs. CC), CG+GG carriers (OR = 1.867, p = 0.057; OR = 1.847, p = 0.055, respectively). CT genotype in IL1B rs1143634 polymorphism associated with 2.33 times elevated risk of autism and showed a significant association compared to wild-type CC genotype (p = 0.02). IL1B rs1143634 polymorphism presented a significantly elevated risk for the development of ASD with recessive model (CC+CT vs.TT), TT genotype (OR = 8.145, p = 0.02). Conclusion This study concludes that rs1143634 is associated with the risk of ASD in Turkish children. Determining these polymorphisms in a larger sample group may contribute to understanding the etiology of ASD and developing new treatment protocols. Abbreviations ASD: Autism spectrum disorder; DNA: Deoxyribonucleic acid; IL6: Interleukin 6; IL1B: Interleukin 1 beta; Real-time PCR: Real-time polymerase chain reaction; JAK-STAT: The Janus kinase/signal transducers and activators of transcription; MAPK: The mitogen-activated protein kinase; 5ʹUTR: The 5′ untranslated region; IL1α: Interleukin 1 alpha; IL-1Ra: Interleukin 1 receptor antagonist; NF-κB: Nuclear factor-kappa B; DSM-V: The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition; M-CHAT: Modified Checklist for Autism in Toddlers; EDTA: Ethylenediaminetetraacetic acid; gDNA: Genomic DNA; HWE: Hardy–Weinberg equilibrium; ANK2: Ankyrin 2; NL3: Neuroligin-3; XRCC4: X-ray repair cross complementing 4

Association between VEGF single nucleotide polymorphism and breast cancer in the Northern China Han population.

To investigate the associations of four commonly studied single nucleotide polymorphisms (SNP) of the vascular endothelial growth factor (VEGF), including -460T/C (rs833061), - 634G/C (rs2010963), - 2578C/A (rs699947), and +936T/C (rs3025039), with the incidence, aggressiveness, and tumor markers expression of breast cancer in the Northern China Han population. Followed the genomic DNA extraction, a total of 259 patients with breast cancer (case group) and 273 healthy women (control group) underwent genotyping by PCR-LDR SNP assays. The associations between VEGF gene polymorphisms and the incidence, aggressiveness, and tumor markers expression of breast cancer were analyzed. Significant differences were observed in allele frequency and genotype distribution of - 634G/C between breast cancer cases and healthy controls (p = 0.006, 0.013). Individuals who carry the G allele more likely had a lower risk of breast cancer (OR, 0.866, 95% CI 0.782-0.959). Compared with CC genotype carriers, women who had the CG and GG genotypes demonstrated a relatively lower risk (OR, 0.860, 95% CI 0.757-0.978, p = 0.022; OR, 0.778, 95% CI, 0.656-0.924, p = 0.004, respectively). When we stratified the group of patients according to the status of tumor markers, a significant association of - 634G/C SNP and Ki-67 expression was observed. The CC genotype carriers were more likely to be characterized by high expression of Ki-67 (p = 0.031). Further analysis showed that the - 460T/-634C/-2578C/+936C haplotype was more associated with a higher risk of breast cancer (OR, 1.445, 95% CI 1.123-1.859, p = 0.004), whereas the - 460T/- 634G/- 2578C/+936C one was associated with a lower risk (OR, 0.736, 95% CI 0.563-0.963, p = 0.025). In the present study, we concluded that VEGF gene - 634G/C polymorphism is related to the incidence of breast cancer in the Han population in Northern China and also might be associated with tumor proliferation index Ki-67.