TA Genotype Research Articles

Pharmacogenomic Study of Selected Genes Affecting Amlodipine Blood Pressure Response in Patients with Hypertension.

Despite the availability of various antihypertensive medications, the response to these medications varies among individuals. Understanding how individual genetic variations affect drugs treatment outcomes is a key area of focus in precision medicine. This study investigated the correlation between single nucleotide polymorphisms (SNPs) in selected genes (CACNA1C, CACNA1D, ABCB1, ACE, ADBR2, and NOS1AP) and the blood pressure (BP) control by amlodipine. Four hundred individuals of Pashtun ethnicity undergoing amlodipine treatment for hypertension were included in the present study and divided into the controlled (BP less than 140/90mmHg) and uncontrolled (BP greater than 140/90mmHg) hypertension groups. Blood samples (3 mL) were collected from each participant, and DNA was extracted using the Kit method. Ten SNPs in amlodipine pharmacogenes were selected and genotyped using real-time PCR with the TaqMan® system. Logistic regression model was used to determine the association between SNPs and the amlodipine BP response. Notable association were observed between SNP rs2239050/CACNA1C and amlodipine blood pressure response, with GG genotype carriers demonstrating a better response (P=0.004) than individuals carrying CC or CG genotypes. SNP rs312481/CACNA1D also exhibited a positive pharmacogenetic association, Individuals with the GG genotype showing a considerable reduction in BP (P=0.021) compared to participants with AA or GA genotypes. In case of SNP rs429/ACE individuals carrying TA genotype were less likely to achieve BP control (P=0.002) than AA genotype carriers. Our finding suggests that the SNPs rs2239050/CACNA1C, rs312481/CACNA1D and rs429/ACE influence amlodipine blood pressure response in patients with hypertension. It is recommended that prior knowledge of amlodipine associated pharmacogenetic variants is important that could improve its treatment outcomes in hypertensive patients.

Genetic change investigation in DOCK1 gene in an Iranian family with sign and symptoms of temporomandibular joint disorder (TMD).

Temporomandibular joint disorder (TMD) is a complex condition with pain and dysfunction in the temporomandibular joint and related muscles. Scientific evidence indicates both genetic and environmental factors play a crucial role in TMD. In this study, we aimed to discover the genetic changes in individuals from 4 generations of an Iranian family with signs and symptoms of TMD and malocclusion Class III. Whole Exome Sequencing (WES) was performed in 4 patients (IV-8, IV-9, V-4, and V-6) with TMD according to (DC/TMD), along with skeletal Class III malocclusion. Then, PCR sequencing was performed on 23 family members to confirm the WES. In the present study, WES results analysis detected 6 heterozygous non-synonymous Single Nucleotide Variants (SNVs) in 5 genes, including CRLF3, DNAH17, DOCK1, SEPT9, and VWDE. A heterozygous variant, c.2012T > A (p.F671Y), in Exon 20 of the DOCK1 (NM_001290223.2) gene was identified. Then, this variant was investigated in 19 other members of the same family. PCR-Sequencing results showed that 7/19 had heterozygous TA genotype, all of whom were accompanied by malocclusion and TMD symptoms and 12/19 individuals had homozygous TT genotype, 9 of whom had no temporomandibular joint problems or malocclusion. The remaining 3 showed mild TMD clinical symptoms. The 5 other non-synonymous SNVs of CRLF3, DNAH17, SEPT9, and VWDE were not considered plausible candidates for TMD. The present study identified a heterozygous nonsynonymous c.2012T > A (p.F671Y) variant of the DOCK1 gene is significantly associated with skeletal class III malocclusion, TMD, and its severity in affected individuals in the Iranian pedigree. The role of genetic factors in the development of TMD has been described. The present study identified a nonsynonymous variant of the DOCK1 gene as a candidate for TMD and skeletal class III malocclusion in affected individuals in the Iranian pedigree.

Study the Association of Fat Mass and Obesity-associated (FTO) Gene Polymorphisms (SNP rs9939609) with Biochemical Markers in Obese Iraqi Patients

This study aimed to evaluate the association of single nucleotide polymorphisms (SNP rs-9939609) of the fat mass and obesity-associated (FTO) gene with body mass index (BMI) and some biochemical markers in obese patients. The fat and mass obesity (FTO) gene variant specific single nucleotide polymorphism (SNP rs-9939609) with the T to A missense mutation may have a powerful association with obesity. This case-control study included 106 obese patients (57 males and 49 females) and 80 healthy control (40 males and 40 females). DNA was extracted from whole blood, and then the tetra-primer amplification refractory mutation system - polymerase chain reactions (ARMS.PCR) technique was used to limit the single nucleotide gene polymorphisms (rs9939609) of the FTO gene. Lipid profile, glycated hemoglobin (HbA1C), fasting blood sugar, insulin and FTO concentrations were measured by standard methods. In this study, the A allele in the rs9939609 was at a higher frequency of 35 (33.1%) in the obese patients and at a significant p-value = 0.039 compared with control 15 (18.7%). It significantly increased in the additive model and allele frequency (p= 0.003, 0.002 respectively). The rs9939608 SNP showed a significant association with increased BMI, insulin and homeostatic model assessment-insulin resistance (HOMO-IR) with p-values of 0.001, 0.001 and 0.028 respectively. After making adjustments for age and sex, lower levels of high-density lipoprotein (HDL) were observed in the AA and TA genotypes compared to the TT genotype (p = 0.004). While, no significant differences were recorded between the rs9939608 SNP and HbA1C, total cholesterol (TC), triglyceride (TG), very low-density lipoprotein (VLDL), and low-density lipoprotein (LDL) in obese patients

Molecular Determination of Tumor Necrosis Factor-alpha, Interleukin-8, Interleukin-10, and C-X-C Chemokine Receptor-2 Genetic Variations and their Association with Disease Susceptibility and Mortality in COVID-19 Patients.

Altered cytokine levels have been associated with poor outcomes among COVID-19 patients. TNF-α, IL-8 and IL-10 are key cytokines in COVID-19 pathogenesis, and CXCR-2 is a major chemokine receptor involved in inflammatory response. Polymorphisms in the genes of these proteins are proposed to influence disease outcomes. In this study, we aimed to find out the association of genetic polymorphisms in TNF-α, IL-8, IL-10 and CXCR-2 genes with susceptibility to and mortality of COVID-19. The present case-control study was conducted on 230 subjects, among whom 115 were clinically diagnosed and RT-PCR-confirmed COVID-19 patients and 115 healthy control subjects. The polymorphisms in TNFα -308 G>A (rs1800629), IL-8 -251T>A (rs4073), CXCR2 +785 C>T (rs2230054) genes were detected by ARMS -PCR assay whereas for IL-10 (-1082 G>A), rs1800896 G>A allele-specific PCR assay was used and their association with COVID-19 susceptibility and mortality was estimated by multivariate analysis. The results were analyzed for risk of infection and mortality through different inheritance models. Frequencies of TNF-α rs1800629 GA, AA, IL-8 rs4073 TA, AA, IL-10 (-1082 G>A), rs1800896 GA and GG, and CXCR2 rs2230054 CT genotypes were significantly higher in COVID-19 patients compared to the control group (p < 0.05). Furthermore, COVID-19 patients had a higher frequency of the polymorphic A allele of TNF-α, the A allele of IL-8, the G allele of IL-10, and the T allele of CXCR2. The risk of susceptibility to COVID-19 was significantly associated with TNF-α rs1800629 GA, GA+AA genotypes and the A allele, IL-8 rs4073 TA, AA genotypes and A allele, IL-10 rs1800872 GA and CC genotypes and C allele, and CXCR2 rs2230054 CT and CT+CC genotypes. TNF-α-GA and AA genotypes and A allele, IL-8 TA and AA genotypes and A allele and CXCR-2 CC and CT genotypes have significant associations with mortality risk in COVID-19 patients, while GA and GG genotypes of the IL-10 are shown to confer significant protection against mortality from COVID-19. The findings of this study provide important insights into the COVID-19 disease and susceptibility risk. The polymorphisms in TNFα -308 G>A (rs1800629), IL-8 -251T>A (rs4073), IL-10 (-1082 G>A), rs1800896 and CXCR2 +785 C>T (rs2230054) are associated with the risk of susceptibility to COVID-19 and with mortality in COVID-19 patients. Further studies with larger sample sizes are necessary to confirm our findings.

Fat Mass and Obesity-Related (FTO) Gene Variant Is a Predictor of CVD in T2DM Patients.

Background: The role of the common FTO gene variant rs9939609 in obesity has been well established, and the FTO gene has a strong association with T2DM. Objective: To investigate the association of FTO gene variant rs9939609 with obesity-related parameters in T2DM and CVD patients. Materials and Methods: In this cross-sectional study, 280 subjects of either sex aged 45.10 ± 9.6 years were randomly divided into four groups, that is, T2DM, T2DM with CVD, nondiabetic with CVD disease, and normal control. These samples were genotyped by ARMS-PCR. The FTO gene association with obesity-related parameters in T2DM and CVD patients was analyzed by SPSS 22. Results: The TT genotype was the most common genotype (46.80%) in our study groups. The minor allele frequency (MAF) was significantly higher in T2DM patients (0.39 vs. 0.28), T2DM patients with CVD (0.43 vs. 0.28), and nondiabetic patients with CVD (0.35 vs. 0.28) as compared to control with p < 0.005. Carriers of the AA genotype of the FTO gene rs9939609 were significantly associated with increased BMI, WC, HbA1C, SBP, DBP, and TGs and lowered HDL cholesterol as compared to the TA and TT genotypes in T2DM and CVD patients with p < 0.005. The FTO gene variant rs9939609 showed a significant association with T2DM and CVD. The AA genotype odds ratio (OR) in T2DM was 1.48 (1.06-2.32), p = 0.006, and in CVD, it was 1.56 (1.04-2.4), p = 0.003. Conclusion: The FTO gene variant rs9939609 has a strong association with T2DM and CVD. The AA genotype of FTO gene variants rs9939609 showed a strong association with most of the risk factors of CVD and T2DM.

المظاهر الوراثية لجين ACTN3 / EXON-19 وارتباطها بأداء خيول الثيربرد في العراق

The research was conducted in the Iraqi Equestrian Club (15 km west of Baghdad city center) for the period from 10/1/2021 to 11/30/2022, with the aim of revealing the ACTN3 gene/ EXON-19 region polymorphism and its relationship to the performance of Thoroughbred horses. British in Iraq. It was found that there are 3 variants (3 SNPs) in the ACTN3 gene with respect to exon 19 and in different sites , which are rs1143578253, their polymorphism are TT, TA, and AA and their distribution ratios were 15.38, 56.41 and 28.21%, and that the non-significant difference, and the frequency of the allele was 0.44 and 0.56 for the two alleles C and T, respectively, and the heterogeneity rs1141508235. It appeared that there were two genotypes of the studied piece in the ACTN3/ EXON19 gene in the thoroughbred horses, CC and CT genotype, with the absence of the TT structure, and the highly significant differences (P≤0.01) between the distribution ratios of the combinations in the British thoroughbred, as the two ratios were 87.18 and 12.82% for the two genotypes CC and TC, and the allelic frequencies for the C and T alleles were 0.94 and 0.06, respectively. The distribution percentages of ACTN3/EXON19 gene polymorphism at position rs1146645613/SNP for the horse sample in this study had high significant differences (P≤0.01) between the genotype's distribution percentages in the British thoroughbred, and the percentages were 87.18 and 12.82% for the two genotypes TT and TC, and the mutant structure did not appear. CC and the frequencies for the T and C alleles were 0.94 and 0.06, respectively. There was a significant variation (P≤0.05) in the depth of respiration after exercise according to the different polymorphism of the rs1143578253 hetero, and the highest rate was for the TT combination (84.80 ± 5.13 seconds) as well as the number of respiration times after exercise, but for the hybrid genotype TA (59.16 ± 1.81 times/min), there was There was a highly significant variation (P≤0.01) in the rate of speed according to the genotype of the thoroughbred horses, and the highest rate of speed was for horses with the mutant genotype AA and the lowest for their counterparts with the wild genotype TT. It is concluded from the study that the ACTN3 gene has a distinct role in some of the traits studied on British terrier horses in Iraq, especially the number and depth of respiration after exercise, rate of speed, and some body measurements, specifically body length, chest circumference, and frontal height, as it varied significantly with the difference in the polymorphism of some variations.

Pharmacogenetics of pediatric acute lymphoblastic leukemia in Uruguay: adverse events related to induction phase drugs.

In Uruguay, the pediatric acute lymphoblastic leukemia (ALL) cure rate is 82.2%, similar to those reported in developed countries. However, many patients suffer adverse effects that could be attributed, in part, to genetic variability. This study aims to identify genetic variants related to drugs administered during the induction phase and analyze their contribution to adverse effects, considering individual genetic ancestry. Ten polymorphisms in five genes (ABCB1, CYP3A5, CEP72, ASNS, and GRIA1) related to prednisone, vincristine, and L-asparaginase were genotyped in 200 patients. Ancestry was determined using 45 ancestry informative markers (AIMs). The sample ancestry was 69.2% European, 20.1% Native American, and 10.7% African, but with high heterogeneity. Mucositis, Cushing syndrome, and neurotoxicity were the only adverse effects linked with genetic variants and ancestry. Mucositis was significantly associated with ASNS (rs3832526; 3R/3R vs. 2R carriers; OR: = 6.88 [1.88-25.14], p = 0.004) and CYP3A5 (non-expressors vs. expressors; OR: 4.55 [1.01-20.15], p = 0.049) genes. Regarding Cushing syndrome, patients with the TA genotype (rs1049674, ASNS) had a higher risk of developing Cushing syndrome than those with the TT genotype (OR: 2.60 [1.23-5.51], p = 0.012). Neurotoxicity was significantly associated with ABCB1 (rs9282564; TC vs. TT; OR: 4.25 [1.47-12.29], p = 0.007). Moreover, patients with <20% Native American ancestry had a lower risk of developing neurotoxicity than those with ≥20% (OR: 0.312 [0.120-0.812], p = 0.017). This study shows the importance of knowing individual genetics to improve the efficacy and safety of acute lymphoblastic leukemia.

Association between GLO1 variants and gestational diabetes mellitus susceptibility in a Chinese population: a preliminary study.

Glyoxalase 1 (GLO1) plays a crucial role in defending against glycation. Single nucleotide polymorphism (SNP) variants in the GLO1 gene may affect gene expression and alter enzyme activity. However, there have been limited studies evaluating the association between GLO1 and diabetes, especially gestational diabetes mellitus (GDM). Therefore, this study is the first to explore the association of GLO1 SNPs and GDM risk. The study included a total of 500 GDM patients and 502 control subjects. The SNPscan™ genotyping assay was used to genotype rs1781735, rs4746 and rs1130534. To assess the disparities in genotype, allele, and haplotype distributions and their correlation with GDM risk, the independent sample t-test, logistic regression, and chi-square test were employed during the data processing phase. Furthermore, one-way ANOVA was conducted to determine the differences in genotype and blood glucose and methylglyoxal(MG) levels. Significant differences were observed in prepregnancy body mass index (pre-BMI), age, systolic blood pressure (SBP), diastolic blood pressure (DBP), and parity between GDM and healthy subjects (P < 0.05). After adjusting for these factors, GLO1 rs1130534 TA remained associated with an increased risk of GDM (TA vs. TT + AA: OR = 1.320; 95% CI: 1.008-1.728; P = 0.044), especially in the pre-BMI ≥ 24 subgroup (TA vs. TT + AA: OR = 2.424; 95% CI: 1.048-5.607; P = 0.039), with fasting glucose levels being significantly elevated in the TA genotype compared to the TT genotype (P < 0.05). Conversely, the GLO1 rs4746 TG was associated with a decreased risk of GDM (TG vs. TT: OR = 0.740; 95% CI: 0.548-0.999; P = 0.049; TG vs. TT + GG: OR = 0.740; 95% CI: 0.548-0.998; P = 0.048). Additionally, the haplotype T-G-T of rs1781735, rs4746 and rs1130534 was associated with a decreased risk of GDM among individuals with a pre-BMI ≥ 24 (OR = 0.423; 95% CI: 0.188-0.955; P = 0.038). Furthermore, the rs1781735 GG genotype was found to be more closely related to maternal MG accumulation and neonatal weight gain (P < 0.05). Our findings suggested that GLO1 rs1130534 was associated with an increased susceptibility to GDM and higher blood glucose levels, but GLO1 rs4746 was associated with a decreased risk of GDM. The rs1781735 has been associated with the accumulation of maternal MG and subsequent weight gain in neonates.

Avrupa Levreğinde (Dicentrarchus labrax) Karnitin Palmitoiltransferaz 1A (CPT1A) Geni Tanımlanması ve Karakterizasyonu

Objective: CPT1A intervenes in the access of the long-chain fatty acyl-CoA to the mitochondrial matrix. In this study, we conducted the genetic polymorphisms of the partial sequence of the CPT1A gene in European sea bass (Dicentrarchus labrax) that were cage cultured in the Aegean Sea.&#x0D; Material and Methods: Genomic DNA was isolated from 100 European sea bass individuals. After amplifying a partial region of the CPT1A gene by thermal cycler, PCR products were sequenced via Sanger method.&#x0D; Results: We detected two SNPs in partial sequence of the CPT1A gene in European sea bass. TT, TA and AA genotypes were observed for CPT1A g.2080T&gt;A locus with frequencies of 27.04, 49.92 and 23.04%, respectively. The frequencies of the g.2216A&gt;G locus as AA, AG and GG were found to be 1.2, 19.58 and 79.21%, respectively. The CPT1A g.2080T&gt;A locus was in HWE, whereas the g.2216A&gt;G locus was not in HWE.&#x0D; Conclusion: European sea bass has a high commercial value. These findings suggest that two SNPs in the CPT1A gene could be used for genomic selection programs related to fatty acid composition in European sea bass.&#x0D; Keywords: Fatty acid, SNP, sea bass, variation

HLA-Cw6 increases the risk of psoriasis and early onset before twenty-seven years of age among the Vietnamese population.

Psoriasis is a chronic inflammatory skin disease that affects people all over the world. It is linked to the HLA-Cw6 allele, which is more common in Caucasians than in Asians and varies across ethnic groups. We investigated the association between the disease severity and the onset age of HLA-Cw6 prevalence in Vietnamese psoriasis patients. In 121 psoriasis patients and 30 healthy controls, we looked at the relationship between HLA-Cw6 and clinical features. We found that patients with psoriasis had significantly higher levels of HLA-Cw6 (64.5%) than controls (26.7%) (p=0.0001), with an odds ratio of 4.98 (2.04-12.15). Positive HLA-Cw6 patients had a significantly lower mean age of psoriasis onset than negative HLA-Cw6 patients. Patients with mild psoriasis (100%) were more likely to have the AA genotype, while patients with moderate to severe psoriasis (47.2% and 59.0%, respectively) and those with high PASI scores (55.1% and 54.1%, respectively) were more likely to have the TA genotype. Thus, HLA-Cw6 is a major genetic risk factor for psoriasis in Vietnamese patients, especially early-onset cases. Variations in HLA-Cw6 genotypes also affect disease severity.

Relationship of the CYP17 gene (T2231A) to milk production and its components in goats

The experiment was conducted at the Ruminant Research Station of the General Authority for Agricultural Research / Ministry of Agriculture on a sample of 53 goats of two breeds (26 Shami goats and 27 local goats), as well as the Scientific Progress Laboratory specialized in biotechnology and genetic material analysis. In order to determine the genotypes and allelic repeats of the CYP17 gene in goats to determine its relationship to milk production and its components, after the completion of the PCR polymerase chain reaction, the results were sent to the Humanizing Genomics Macrogen Company in South Korea to detect the genotypes of the studied area using the sequencing technology, Two genotypes TT and TA were obtained at the site (T2231A), and the percentage of TT genotype was 26.92% for Shami goats. The percentage of TA genotype was 73.08, and the relationship between them was significant (P≥0.05). The allelic frequency of the T allele was And A 0.63 and 0.37, respectively, where the results showed a significant relationship (P≥0.05) between the genotypes and the amount of total milk production and the percentage of solids that are not fatty. The animals carrying the TT genotype recorded the highest amount of production than those carrying the TA genotype, 571.08 ± 48.69 and 432.24 ± 50.56, respectively. Also, the animals carrying the TT genotype outperformed the animals carrying the TA genotype in the percentage of solid non-fat components, which scored 12.79 ± 1.66, and they scored 9.89 ± 1.63. The percentage of TT genotype for domestic goats was 40.74%, and the percentage of genotype TA was 59.26. the relationship between them was significant (P≥0.05), and the allelic frequency of the T and A alleles was 0.70 and 0.30, respectively. The results also showed a significant relationship (P≥0.05) between the genotypes and the amount of total milk production of the local goats, where the animals carrying the TT genotype recorded the highest amount of production than the animals carrying the TA genotype, and it scored 548.15 ± 72.06 and 350.10 ± 47.94, respectively. Thus, the CYP17 gene can be used in genetic improvement programs. Keywords: Goats; CYP17 Gene; Genotype; Milk Production.

Association of Cd40 (rs1883832) SNP in some Iraqi patients with Rheumatoid Arthritis and their correlation with disease activity

Objective: To determine the genotyping of CD40 gene (rs1883832) single nucleotide polymorphism (SNP) amongrheumatoid arthritis patients, and to investigate its correlation with disease activity.Method: The case-control study was conducted at Baghdad Teaching Hospitals, its affiliated Rheumatology units andAl-Yarmouk Teaching Hospital, Baghdad, Iraq, from July 2020 to May 2021, and comprised adult females withrheumatoid arthritis in group A and healthy controls in group B. The disease activity in group A was evaluated usingthe Disease Activity Score in 28 Joints scale. Samples from both groups were genotyped using TaqMan Assay for clusterof differentiation gene rs1883832 single nucleotide polymorphism. Data was analysed using SPSS 28.Results: Of the 118 participants, 76(64.4%) were in group A with mean age 45.38±1.23 years, and 42(35.6%) were incontrol group B with mean age 46.48±2.02 years. At cluster of differentiation gene rs1883832 single nucleotidepolymorphism, there was a non-significant difference in the frequency of T and A alleles as well as in TT, AA and TA ingroup A patients compared to group B controls (p&gt;0.05). Rheumatoid factor and C-reactive protein concentrationswith TT, TA and AA genotypes in group A were significantly higher in group A compared to group B (p&lt;0.05). Withingroup A, there was a significant increase in the TT genotype and a significant decrease in the TA genotype in severecases compared to mild cases. (p&lt;0.05).Conclusion: The cluster of differentiation gene rs1883832 single nucleotide polymorphism T allele was found to be arisk factor for rheumatoid arthritis and disease severity. The TT and AA alleles acted as protective factors.Keywords: Polymorphism, Disease activity, Genotype.

Association between genetic variants of TLR2, TLR4, TLR9 and schizophrenia

Background and study aimSchizophrenia (SZ) is a multifactorial disorder involving complex interactions between genetic and environmental factors, where immune dysfunction plays a key etiopathogenic role. In order to explore the control of innate immune responses in SZ, we aimed to investigate the potential association between twelve TLR2, TLR4 and TLR9 variants (TLR2: rs4696480T>A, rs3804099T>C, rs3804100T>C; TLR4: rs1927914G>A, rs10759932T>C, rs4986790A>G, rs4986791T>C, rs11536889G>C, rs11536891T>C; TLR9: rs187084A>G, rs352139T>C and rs352140C>T) and SZ susceptibility in a Tunisian population. Patients and methodsThis study included 150 patients and 201 healthy controls with no history of psychiatric illness. Genotyping was done using a TaqMan SNP genotyping assay. We also assessed a haplotype analysis for TLR2, TLR4 and TLR9 variants with SZ using Haploview 4.2 Software. ResultsWe found that the AA genotype of the TLR2 rs4696480T>A variant was significantly associated with an increased risk of SZ (46% vs. 31%, P=4.7×10−3, OR=1.87 and 95% CI [1.18–2.97]). The frequency of the TA genotype was significantly higher in the control group than in SZ patients (27% vs. 43%, P=2.1×10−3) and may be associated with protection against SZ (OR=0.49 and 95% CI [0.30–0.80]). Whereas, the TLR9 rs187084-GG genotype was higher in the control group compared to patients (16% vs. 5%, P=1.6×10−3) and would present protection against SZ (OR=0.28, CI=[0.10–0.68]). The ACT haplotype of the TLR2 and the ACC haplotype of the TLR9 gene were identified as a risk haplotypes for SZ (P=0.04, OR=9.30, 95% CI=[1.11–77.71]; P=3×10−4, OR=6.05, 95% CI=[2.29–15.98], respectively). ConclusionThe results indicate that TLR2 and TLR9 genetic diversity may play a role in genetic vulnerability to SZ. However, including more patients and evaluation of TLR2 and TLR9 expression are recommended.

Genome-wide interaction analysis of folate for colorectal cancer risk

BackgroundEpidemiological and experimental evidence suggests that higher folate intake is associated with decreased colorectal cancer (CRC) risk; however, the mechanisms underlying this relationship are not fully understood. Genetic variation that may have a direct or indirect impact on folate metabolism can provide insights into folate’s role in CRC. ObjectivesOur aim was to perform a genome-wide interaction analysis to identify genetic variants that may modify the association of folate on CRC risk. MethodsWe applied traditional case-control logistic regression, joint 3-degree of freedom, and a 2-step weighted hypothesis approach to test the interactions of common variants (allele frequency >1%) across the genome and dietary folate, folic acid supplement use, and total folate in relation to risk of CRC in 30,550 cases and 42,336 controls from 51 studies from 3 genetic consortia (CCFR, CORECT, GECCO). ResultsInverse associations of dietary, total folate, and folic acid supplement with CRC were found (odds ratio [OR]: 0.93; 95% confidence interval [CI]: 0.90, 0.96; and 0.91; 95% CI: 0.89, 0.94 per quartile higher intake, and 0.82 (95% CI: 0.78, 0.88) for users compared with nonusers, respectively). Interactions (P-interaction < 5×10-8) of folic acid supplement and variants in the 3p25.2 locus (in the region of Synapsin II [SYN2]/tissue inhibitor of metalloproteinase 4 [TIMP4]) were found using traditional interaction analysis, with variant rs150924902 (located upstream to SYN2) showing the strongest interaction. In stratified analyses by rs150924902 genotypes, folate supplementation was associated with decreased CRC risk among those carrying the TT genotype (OR: 0.82; 95% CI: 0.79, 0.86) but increased CRC risk among those carrying the TA genotype (OR: 1.63; 95% CI: 1.29, 2.05), suggesting a qualitative interaction (P-interaction = 1.4×10-8). No interactions were observed for dietary and total folate. ConclusionsVariation in 3p25.2 locus may modify the association of folate supplement with CRC risk. Experimental studies and studies incorporating other relevant omics data are warranted to validate this finding.

Intronic variants of LGALS13 gene encoding placental protein (PP13) are linked with increased risk of infection-associated spontaneous preterm birth.

Spontaneous preterm birth (sPTB) is a global health issue. Studies suggest infection and infection-based inflammatory responses are major risk factors for sPTB. Considering the important role of anti-inflammatory proteins in pregnancy, the study aimed to find the association between anti-inflammatory LGALS13 gene variants IVS2-22 A/G (rs2233706) and IVS3+72 T/A (rs2233708) and the risk of sPTB during Chlamydia trachomatis, Mycoplasma hominis and Ureaplasma urealyticum infection in Indian population. Placental samples of 160 sPTB and 160 term women were collected. Pathogens were detected by PCR. The genotyping of LGALS13 gene variants IVS2-22 A/G (rs2233706) and IVS3+72 T/A (rs2233708) was done by qualitative real-time PCR using allelic discrimination method (VIC- and FAM-labeled). The frequency of AG or GG genotype of LGALS13 IVS2-22A/G polymorphism (rs2233706) was 75.5% in infected sPTB cases and 14.4% in uninfected sPTB cases and 7.3% in term birth controls (p<.0001), while the frequency of TA or AA genotype of LGALS13 IVS3+72T/A polymorphism (rs2233708) was 83.6% in infected sPTB cases and 18% in uninfected sPTB cases and 12.7% in term birth controls (p<.0001). The genotypic frequencies for both the variants of LGALS13 were statistically significant (p<.0001) in the infected sPTB versus uninfected sPTB and term birth controls. Study reveals strong association between the presence of immunological gene variants LGALS13 IVS2-22 A/G (rs2233706) and LGALS13 IVS3+72 T/A (rs2233708) and risk of sPTB during C. trachomatis, M. hominis and U. urealyticum infection.

SCN1A Polymorphisms and Haplotypes Are Associated With Valproic Acid Treatment Outcomes in Chinese Children With Epilepsy

BackgroundSodium channel genes, especially SCN1A, were reported to play an important role in the treatment outcomes of antiseizure medications. The aim of this study was to explore the association of SCN1A polymorphisms with efficacy and adverse drug reactions (ADRs) related to valproic acid (VPA) among Chinese children with epilepsy. MethodsA total of 126 children with epilepsy treated with VPA for at least 12 months were enrolled in this study. Three single nucleotide polymorphisms (SNPs) of SCN1A including rs2298771, rs10167228, and rs3812718 were genotyped using Sequenom MassArray system. Bioinformatics tools were used to explore the potential targets and pathways of SCN1A in VPA-related ADRs. ResultsThe three SNPs in this study were found to be closely associated with treatment outcomes for VPA. Carriers of SCN1A rs3812718 TT genotype tended to be seizure-free with VPA treatment (P = 0.007). AA genotype of rs10167228 and TT genotype of rs2298771 might be protective factors for weight gain induced by VPA, whereas TA genotype of rs10167228 and CT genotype of rs2298771 increased the risk. TAT haplotype carriers were found to respond better to VPA treatment (P = 0.017), whereas CTC haplotype might be a risk factor for VPA-induced weight gain (P = 0.035). Bioinformatics analysis suggested that SCN1A might play a role in VPA-induced weight gain by regulating gated channel activity and GABAergic synapse pathway. ConclusionThis study revealed that SCN1A rs2298771, rs10167228, and rs3812718 polymorphisms and haplotypes might affect the treatment outcomes of VPA in Chinese children with epilepsy.

Relationship Between FKBP5 Polymorphisms at Rs1334894, Rs9394309, and Rs6912833 Loci, and Dyslipidemia in Pediatric Nephrotic Syndrome

Background: This study aimed to investigate the relationship between rs1334894, rs9394309, and rs6912833 polymorphisms in <I>FKBP5</I> and hyperlipidemia in nephrotic syndrome (NS). Methods: The case group included 74 children with primary NS, while the control group included 76 healthy children. Polymerase chain reaction and gene sequencing were used to detect polymorphisms at the rs1334894, rs9394309, and rs6912833 loci of <I>FKBP5,</I> in children with NS. Clinical data of total cholesterol (CHOL), triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and plasma albumin were collected. Correlations between <I>FKBP5</I> polymorphisms and serum lipid levels were analyzed during the active period of the disease. Results: A significant difference in LDL levels between the AA and TA genotypes was observed at the rs6912833 locus of <I>FKBP5</I> in the case group, but no statistical difference in CHOL, TG, and HDL levels between these genotypes was found. No statistically significant differences in LDL levels between the AA and TA genotypes, and among the steroid-sensitive, -dependent, and -resistant groups were noted. Moreover, no statistically significant differences in the CHOL, TG, HDL, and LDL levels were observed between TT and TC genotypes at the rs1334894 locus. Conclusion: The AA genotype at the rs6912833 locus of <I>FKBP5</I> may be correlated with plasma lipid levels (LDL) in PNS patients.

Demographic, clinical and genetic factors associated with COVID-19 disease susceptibility and mortality in a Kurdish population.

Coronavirus disease 2019 (COVID-19) is a devastating pandemic that causes disease with a variability in susceptibility and mortality based on variants of various clinical and demographic factors, including particular genes among populations. Determine associations of demographic, clinical, laboratory, and single nucleotide polymorphisms in the ACE2, TMPRSS2, TNF-α, and IFN-γ genes to the incidence of infection and mortality in COVID-19 patients. Prospective cohort study SETTINGS: Various cities in the Kurdistan Region of Iraq. This prospective cohort study compared laboratory markers (D-dimer, tumor necrosis factor-alpha [TNF-α], interferon-gamma [IFN-γ], C-reactive protein [CRP], lymphocyte and neutrophil counts) between COVID-19 patients and healthy controls. DNA was extracted from blood, and genotypes were done by Sanger sequencing. Single nucleotide polymorphisms of the ACE2, TMPRSS2, TNF-α, and IFN-γ genes and demographic characteristics and laboratory markers for predicting mortality in COVID-19. 203 (153 COVID-19 patients, 50 health control subjects). Forty-eight (31.4%) of the COVID-19 patients died. Age over 40 and comorbidities were risk factors for mortality, but the strongest associations were with serum IFN-γ, the neutrophil-to-lymphocyte ratio (NLR), and serum TNF-α. The AA genotype and A allele of TMPRSS2 rs2070788 decreased while the GA genotype and A allele of TNF-α increased susceptibility to COVID-19. Patients with the GA genotype of TNF-α rs1800629 had shorter survival times (9.9 days) than those carrying the GG genotype (18.3 days) (P<.0001 by log-rank test). The GA genotype versus the GG genotype was associated with higher levels of serum TNF-α. The GA genotype increased mortality rates by up to 3.8 fold. The survival rate for COVID-19 patients carrying the IFN-γ rs2430561 TT genotype (58.5%) was lower than in patients with the TA and AA genotypes (80.3%). The TT genotype increased the risk of death (HR=3.664, P<.0001) and was linked to high serum IFN-γ production. Olfactory dysfunction was a predictor of survival among COVID-19 patients. Age older than 40, comorbidities, the NLR and particular genotypes for and the IFN-γ and TNF-α genes were risk factors for death. Larger studies in different populations must be conducted to validate the possible role of particular SNPs as genetic markers for disease severity and mortality in COVID-19 disease. Small sample size. None.

Genetic polymorphisms of MRPS30-DT and NINJ2 may influence lung cancer risk.

Lung cancer is one of the malignant tumors, and genetic background is a risk factor in lung cancer that cannot be neglected. In this study, we aimed to find out the effect of MRPS30-DT and NINJ2 variants on lung cancer risk. In this study, the seven selected single-nucleotide polymorphisms (SNPs) of MRPS30-DT and NINJ2 were genotyped in 509 lung cancer patients and 501 healthy controls based on the Agena MassARRAY platform. Odds ratios and 95% confidence intervals were calculated by logistic regression analysis to evaluate association between gene polymorphisms and lung cancer risk. False-positive report probability was also used to assess false-positive results. Furthermore, the interaction between SNPs was analyzed by multifactor dimensionality reduction to predict lung cancer risk. We identified the genotype TA of rs16901963 (T < A) in MRPS30-DT as a protective factor against lung cancer, while rs16901963-TT was significantly associated with an increased risk of lung cancer. We also revealed that the effect of MRPS30-DT and NINJ2 variants on the risk of lung cancer was dependent on age, gender, smoking, and drinking status. In conclusion, this study first proved that MRPS30-DT and NINJ2 variants played important roles in affecting the susceptibility to lung cancer.

A Rapid Screening Assay for Clarithromycin-Resistant Mycobacterium avium Complex Using Melting Curve Analysis with Nonfluorescent Labeled Probes.

Mycobacterium avium complex (MAC) thrives in various environments and mainly causes lung disease in humans. Because macrolide antibiotics such as clarithromycin or azithromycin are key drugs for MAC lung disease, the emergence of macrolide-resistant strains prevents the treatment of MAC. More than 95% of macrolide-resistant MAC strains are reported to have a point mutation in 23S rRNA domain V. This study successfully developed a melting curve assay using nonfluorescent labeled probes to detect the MAC mutation at positions 2058 to 2059 of the 23S rRNA gene (AA genotype, clarithromycin susceptible; TA, GA, AG, CA, AC, and AT genotypes, clarithromycin resistant). In the AA-specific probe assay, the melting peak of the DNA fragment of the AA genotype was higher than that of DNA fragments of other genotypes. Melting temperature (Tm) values of the AA genotype and the other genotypes were about 80°C and 77°C, respectively. DNA fragments of each genotype were identified correctly in six other genotype-specific probes (TA, GA, AG, CA, AC, and AT) assays. Using genomic DNA from six genotype strains of M. avium and four genotype strains of M. intracellulare, we confirmed that all genomic DNAs could be correctly identified as individual genotypes according to the highest Tm values among the same probe assays. These results indicate that this melting curve-based assay is able to determine MAC genotypes at positions 2058 to 2059 of the 23S rRNA gene. This simple method could contribute to the rapid detection of clarithromycin-resistant MAC strains and help to provide accurate drug therapy for MAC lung disease. IMPORTANCE Since macrolide antibiotics such as clarithromycin or azithromycin are key drugs in multidrug therapy for Mycobacterium avium complex (MAC) lung diseases, the rapid detection of macrolide-resistant MAC strains has important implications for the treatment of MAC. Previous studies have reported a correlation between drug susceptibility testing and the mutation of macrolide resistance genes. In this study, we developed a novel melting curve-based assay using nonfluorescent labeled probes to identify both clarithromycin-resistant M. avium and M. intracellulare with mutations in the 23S rRNA gene, which is the clarithromycin or azithromycin resistance gene. This assay contributed to not only the detection of MAC mutations but also the determination of all genotypes at positions 2058 to 2059 of the 23S rRNA gene. Furthermore, because nonfluorescent labeled probes are used, this assay is more easily and more immediately available than other methods.