Allele Of Rs9939609 Research Articles

Functional SNP in stem of mir-146a affects Her2 status and breast cancer survival.

In-silico investigation suggested a common variant within stem of miR-146a-5p precursor (rs2910164, n.60C>G) associated with breast cancer (BC) phenotypes. Our aim was computationally predicting possible targets of miR-146a-5p and probable rs2910164 mechanism of action in expression of phenotypes in BC. Additionally, a case-control study was designated to examine experimentally the correlation of mir-146a rs2910164 variant and BC phenotypes. In this study, 152 BC subjects and healthy controls were genotyped using RFLP-PCR. Allelic and genotypic association and Armitage's trend tests were run to investigate the correlation between the alleles and genotypes and expressed phenotypes of BC. Bioinformatics analyses introduce regulatory function of miR-146a-5p in numerous signaling pathways and impact of allele substitution upon mir-146a stem-loop stability. Logistic regression data represented the C allele of rs2910164 (OR = 4.00, p= 0.0037) as the risk allele and associated with Her2-positive phenotype. In a similar vein, data revealed the correlation of the C allele and cancer death less than two years in BC patients (OR = 2.65, p= 0.0217). Ultimately, unconditional logistical regression models suggested log-additive model for inheritance manner of rs2910164 in either Her2 status or BC survival (OR = 5.64, p= 0.0025 and OR = 3.13, p= 0.019, respectively). Using bioinformatics connected association of Her2 status to altered function of miR-146a-5p in regulation of focal adhesion and Ras pathway. Furthermore, computations inferred the association between death phenotype and studied SNP upon specific target genes of miR-146a-5p involved in focal adhesion, EGF receptor, Ras, ErbB, interleukin, Toll-like receptor, NGF, angiogenesis, and p53 feedback loops 2 signaling pathways. These verdicts may enhance our perceptions of how mir-146a rs2910164 affect expressed phenotypes in BC, and might have potential implications to develop BC treatment in future.

Dietary fat intake modifies the influence of the FTO rs9939609 polymorphism on adiposity in adolescents: The HELENA cross-sectional study

Background and aimsThe fat mass and obesity associated gene (FTO) has been associated with obesity and dietary intake. The aims were: (i) To assess whether energy and macronutrient intakes were different across the FTOrs9939609 genotypes in adolescents, and (ii) to explore whether dietary fat intake modified the association of the rs9939609 polymorphism with adiposity. Methods and resultsThe FTOrs9939609 polymorphism was genotyped in 652 adolescents (53% females, 14.8 ± 1.2 years, TT = 246, TA = 296, AA = 110). Energy and macronutrient intake were assessed by two non-consecutive 24 h-recalls. Weight, height, waist circumference and skinfold thicknesses were measured and body fat percent was calculated. Energy and macronutrient intake were similar across the FTOrs9939609 genotypes (P > 0.2). There were significant interactions between the FTO polymorphism and fat intake on adiposity estimates (P < 0.05). In adolescents whose fat intake was below 30% (N = 203), the A allele of rs9939609 was not associated with adiposity indices. In contrast, in adolescents whose fat intake was between 30% and 35% of energy (N = 190), the rs9939609 polymorphism was associated with a 1.9% higher body fat per risk allele (95%CI: 0.39, 3.33; P < 0.05), and in those whose fat intake was higher than 35% (N = 259), it was associated with a 2.8% higher body fat per risk allele (95%CI: 1.27, 4.43; P < 0.001). ConclusionsThese findings support the concept that the deleterious effect of the FTOrs9939609 polymorphism on adiposity is exacerbated in adolescents consuming high fat diets. In contrast, the consumption of low fat diets (<30% of energy) may attenuate the genetic predisposition to obesity in risk allele carriers.

A single-nucleotide polymorphism in the MicroRNA-146a gene is associated with diabetic nephropathy and sight-threatening diabetic retinopathy in Caucasian patients.

This study aimed to investigate whether the single-nucleotide polymorphism (SNP) rs2910164 residing within microRNA-146a (miR-146a) is associated with diabetic microvascular complications diabetic nephropathy (DN), proliferative diabetic retinopathy (PDR) or diabetic macular oedema (DME) in either Caucasian patients with type 1 (T1DM) or type 2 (T2DM) diabetes mellitus. Caucasian patients with T1DM (n=733) or T2DM (n=2215) were recruited from ophthalmology, renal and endocrine clinics in Australia and the UK. Patients with T2DM were required to have diabetes mellitus (DM) for at least 5years and be on treatment with oral hypoglycaemic drugs or insulin. In total, 890 participants had DN (168 with T1DM and 722 with T2DM), 731 had PDR (251 with T1DM and 480 with T2DM) and 1026 had DME (170 with T1DM and 856 with T2DM). Participants were genotyped for SNP rs2910164 in miR-146a. Analyses investigating association were adjusted for relevant clinical covariates including age, sex, DM duration, HbA1c and hypertension. A significant association was found between the C allele of rs2910164 and DN in the T1DM group (OR 1.93; CI 1.23-3.03; P=0.004), but no association found in the T2DM group (OR 1.05; CI 0.83-1.32; P=0.691). In the subset of T2DM patients, the C allele was specifically associated with DME (OR 1.25; CI 1.03-1.53; P=0.025). No association with DME was found in the T1DM group (OR 0.87; CI 0.54-1.42); P=0.583), or with PDR for either type of DM. Rs2910164 is significantly associated with microvascular complications DN in patients with T1DM and DME in patients with T2DM.

Combined effects of FTO rs9939609 and MC4R rs17782313 on elevated nocturnal blood pressure in the Chinese Han population.

SummaryAimIn this study we investigated the association of FTO rs9939609 and MC4R. rs17782313 with elevated blood pressure in the Chinese Han population, and analysed the relationship between the rs9939609 and rs17782313 variants.MethodsWe tested the rs9939609 and rs17782313 variants with the sequence-retrieval method.ResultsThe increase in odds ratios of the A allele of rs9939609 and the C allele of rs17782313 for nocturnal blood pressure were 1.37 and 1.69. The nocturnal blood pressure of participants simultaneously carrying the A and C alleles was significantly higher than the blood pressure of those carrying neither FTO nor MC4R risk alleles (p < 0.05), and that of the controls carrying only the A or C alleles (p < 0.05). No association between the FTO or MC4R genes with daytime hypertension was found in this Chinese population (p > 0.05).ConclusionOur data suggest that the rs9939609 and rs17782313 variants may be significantly associated with nocturnal but not daytime blood pressure levels and their combined effects were significant in this Chinese Han population.

Diabetes-Associated Variation in TCF7L2 Is Not Associated With Hepatic or Extrahepatic Insulin Resistance.

A common genetic variation in TCF7L2 is associated with type 2 diabetes. However, the mechanism by which this occurs remains elusive. In addition to affecting insulin secretion, genetic variation at the TCF7L2 locus may alter insulin action or directly modify hepatic glucose metabolism. We sought to determine whether the diabetes-associated variant in this locus (the T allele of rs7903146) increases fasting endogenous glucose production (EGP), and impairs insulin-induced suppression of EGP and insulin-stimulated glucose disappearance. To address this, we studied individuals who were either homozygous for the diabetes-associated allele (TT) at rs7903146 or were homozygous for the protective allele (CC). Subjects were matched for other anthropometric characteristics and were studied using a euglycemic clamp. EGP and glucose uptake were measured using the tracer dilution technique, and the relative contribution of gluconeogenesis to EGP was quantitated using deuterated water corrected for transaldolase exchange. We report that the diabetes-associated variation in TCF7L2 did not associate with fasting EGP, insulin-induced suppression of EGP, and insulin-induced stimulation of glucose uptake. There was no association with the contribution of gluconeogenesis and glycogenolysis to EGP. These data indicate that genetic variation at TCF7L2 does not predispose an individual to type 2 diabetes by altering either hepatic or extrahepatic insulin action.

Association between polymorphisms in pre-miRNA genes and risk of lung cancer in a Chinese non-smoking female population

BackgroundMicroRNAs play important roles in the development of human chronic diseases including lung cancer. This is the first case-control study of lung cancer in a non-smoking female population in northeast China, to evaluate the roles of the polymorphisms in pre-miRNAs on risk of lung cancer. MethodsThe genotypes of six polymorphisms in miRNAs were determined in 575 patients with lung cancer and 608 healthy controls who were frequency matched for age. ResultsFor miR-146a rs2910164, individuals carrying heterozygous CG or homozygous GG genotype had decreased risks of lung cancer compared with those carrying homozygous wild CC genotype (adjusted odds ratios were 0.76 and 0.64, 95% confidence intervals were 0.59–0.99 and 0.46–0.90, P values were 0.039 and 0.010, respectively). G allele of rs2910164 was associated with a lower risk of lung cancer with a significant odds ratio of 0.80. MiR-423 rs6505162CA or AA genotype was associated with significantly decreased risk for lung cancer compared to CC genotype (adjusted odds ratios were 0.77 and 0.54). The significant result was also found in the allele model with odds ratio of 0.75. However, miR-196a2 rs11614913, miR-30c-1 rs928508, miR-608 rs4919510 and miR-27a rs895819 polymorphisms were not significantly associated with lung cancer risks in any models. The similar results were also found in lung adenocarcinoma patients. ConclusionsThese findings suggest that miR-146a rs2910164C>G and miR-423 rs6505162C>A polymorphisms may contribute to genetic susceptibility to lung cancer and lung adenocarcinoma in Chinese non-smoking females.

Correlation Between CASC8, SMAD7 Polymorphisms and the Susceptibility to Colorectal Cancer: An Updated Meta-Analysis Based on GWAS Results.

Genome-wide association studies (GWASs) and a number of case–control studies have suggested that several single nucleotide polymorphisms (SNPs), rs7837328, rs7014346, rs6983267, rs10505477 on CASC8 gene and rs4939827, rs4464148, rs12953717 on SMAD7 gene are significantly correlated with the susceptibility to colorectal cancer (CRC). For the sake of clarifying the association, a meta-analysis was conducted and population heterogeneity was considered in the study.A total of 34 articles including 90 studies (168,471 cases and 163,223 controls) that evaluated the relationship between the CASC8, SMAD7 genes and the risk of CRC under the allelic model were reviewed. Also subgroup analysis was performed by ethnicity (Caucasian, Asian, and African) and all of the analyses were implemented in R 3.2.1 software.Pooled data from the meta-analysis revealed that the A allele of rs7837328, the A allele of rs7014346, the G allele of rs6983267, the A allele of rs10505477, the T allele of rs4939827, the T of rs4464148, and the T of rs12953717 were significantly associated with an increased risk of CRC under the allelic model. Additionally, subgroup analyses of 6 SNPs by ethnicity (rs4464148 excepted) witnessed that the A allele of rs7837328, the G allele of rs6983267, and the T of rs12953717 were notably associated with an increased risk of CRC among Caucasian and Asian. Furthermore, the A allele of rs7014346, the A allele of rs10505477, and the T allele of rs4939827 were significantly related with an elevated risk of CRC only among Caucasian.Our study suggested that for CASC8 gene, SNP of rs7837328 and rs6983267 are risk factors for CRC among both Caucasian and Asian whereas rs7014346 and rs10505477 are risky gene polymorphisms only among Caucasian. For SMAD7 gene, rs4939827 and rs4464148 are risk factors for CRC among Caucasian whereas rs12953717 could elevate the susceptibility to CRC in both Caucasian and Asian.

Association of the microRNA-Single Nucleotide Polymorphism rs2910164 in miR146a with sporadic breast cancer susceptibility: A case control study

Breast cancer (BC) is primarily considered a genetic disorder with a complex interplay of factors including age, gender, ethnicity, family history, personal history and lifestyle with associated hormonal and non-hormonal risk factors. The SNP rs2910164 in miR146a (a G to C polymorphism) was previously associated with increased risk of BC in cases with at least a single copy of the C allele in breast cancer, though results in other cancers and populations have shown significant variation. In this study, we examined this SNP in an Australian sporadic breast cancer population of 160 cases and matched controls, with a replicate population of 403 breast cancer cases using High Resolution Melting. Our analysis indicated that the rs2910164 polymorphism is associated with breast cancer risk in both primary and replicate populations (p=0.03 and 0.0013, respectively). In contrast to the results of familial breast cancer studies, however, we found that the presence of the G allele of rs2910164 is associated with increased cancer risk, with an OR of 1.77 (95% CI 1.40-2.23). The microRNA miR146a has a potential role in the development of breast cancer and the effects of its SNPs require further inquiry to determine the nature of their influence on breast tissue and cancer.

Meta-Analysis of miR-146a Polymorphisms Association with Coronary Artery Diseases and Ischemic Stroke.

Coronary artery disease (CAD) and ischemic stroke (IS) are manifestations of atherosclerosis, with a high death rate. miR-146a is a microRNA that participates in the progress of CAD and IS. A single nucleotide polymorphism (SNP) in the precursor of miR-146a, rs2910164, was found to be associated with the risks of CAD and IS. However, the results were inconsistent and inconclusive. A meta-analysis was performed to assess the relationship of rs2910164 and CAD as well as IS susceptibility. The database Pubmed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Chinese National Knowledge Infrastructure (CNKI), and Chinese Biomedical Literature Database (CBM) were searched for related studies. Crude odds ratios with 95% confidence intervals were used to investigate the strength of the association by random- or fixed-effect model. A total of eight studies, with 3138 cases and 3097 controls were identified for the meta-analysis. The results shows that rs2910164 is associated with the risk of CAD significantly in allelic model (OR = 0.86), homozygous model (OR = 0.70), heterozygous model (OR = 0.80) and dominant model (OR = 0.76). The subjects carrying the GG genotype, GG + GC genotype or G allele are at lower risks of CAD. For the susceptibility of IS, there are no significant associations between rs2910164 and total studies. However, in subgroup analysis by sample size and ethnicity, the GG, GG + GC and G allele of rs2910164 are found to be associated with higher risks of IS in large sample size group and in Koreans, under homozygous and dominant models. In conclusion, the current meta-analysis suggests lower risks of CAD for GG, GG + GC genotype and G allele of rs2910164, while rs2910164 is not associated with the risk of IS. Thus rs2910164 might be recommended as a predictor for susceptibility of CAD, but not IS.

A single nucleotide polymorphism in primary-microRNA-146a reduces the expression of mature microRNA-146a in patients with Alzheimer's disease and is associated with the pathogenesis of Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder and is the most common form of dementia among the aging population. Although the incidence of the disease continues to increase, no cure has been developed. Effective treatment is restricted not only due to the lack of curative medicine, but also due to limited understanding of the underlying mechanisms and the diffculties in accurately diagnosing AD in its earliest stages prior to clinical symptoms. Micro (mi) RNAs (miR) have gained increasing attention in the investigation of neurodegenerative diseases. Previous reports have demonstrated that deregulation of miR-146a-5p is associated with the pathogenesis of human AD. In the present study, the coding region of primary (pri)-miR-146a in patients with AD was scanned and the rare C allele of rs2910164 was found to be associated with AD. Using reverse transcription quantitative polymerase chain reaction, it was demonstrated that site variation reduced the expression of mature miR-146a-5p. Notably, a reduction in the expression of miR-146a-5p led to less effcient inhibition of target genes, including Toll-like receptor (TLR)2, which is important in the pathogenesis of AD. Biological function investigations in RAW264.7 cells indicated that, compared with the G allele, the rare C allele upregulated the expression of tumor necrosis factor-α following stimulation with β-amyloid. These findings suggested that one common polymorphism in pri-miR-146a may contribute to the genetic predisposition to AD by disrupting the production of miR-146a-5p and affecting the expression and function of TLR2.

Rs1801133C>T polymorphism in MTHFR is a risk factor for nonsyndromic cleft lip with or without cleft palate in the Brazilian population.

The MTHFR rs1801131A>C and rs1801133C>T variants have been analyzed as putative genetic risk factors for oral clefts within various populations worldwide. To test the role of these polymorphisms in nonsyndromic cleft lip with or without cleft palate (NSCL/P) in the Brazilian population, we conducted a study combining a Family-Based Association Test (transmission disequilibrium test) and a structured association analysis (case-control study) based on the individual ancestry proportions. The rs1801131 and rs1801133 were initially analyzed in 197 case-parent trios by transmission disequilibrium test, and polymorphisms showing significant association with NSCL/P were subsequently studied in independent sample composed of 318 isolated samples of NSCL/P and 598 healthy controls in a case-control approach. Genomic ancestry was characterized by a set of 40 biallelic short insertion/deletion markers. A strong overtransmission of the T allele of rs1801133 was observed in case-parent trios of NSCL/P (p = 0.002), but no preferential parent-of-origin transmission was detected. No association of rs1801131 polymorphism with NSCL/P was observed. The structured case-control analysis supported that the T allele was significantly more frequent in the NSCL/P group (odds ratio: 1.37; 95% CI: 1.12-1.69; p = 0.002) than in the control group. Both polymorphisms were in linkage disequilibrium (D' = 0.94 and r(2) = 0.79), and haplotype-transmission disequilibrium test for allelic combination of rs1801131 and rs1801133 showed a significant overtransmission of haplotype A-T to the affected NSCL/P offspring (p = 0.001). Our findings provide evidences for the involvement of rs1801133 in the development of NSCL/P in the Brazilian population.

Effects of Two Common Polymorphisms rs2910164 in miR-146a and rs11614913 in miR-196a2 on Gastric Cancer Susceptibility.

Background. Single nucleotide polymorphisms (SNPs) in genes encoding microRNAs may play important role in the development of gastric cancer. It has been reported that common SNPs rs2910164 in miR-146a and rs11614913 in miR-196a2 are associated with susceptibility to gastric cancer. The published results remain inconclusive or even controversial. A meta-analysis was conducted to quantitatively assess potential association between the two common SNPs and gastric cancer risk. Methods. A comprehensive literature search was performed in multiple internet-based electronic databases. Data from 12 eligible studies were extracted to estimate pooled odds ratios (ORs) and 95% confidence intervals (95% CI). Results. C allele of rs2910164 is associated with reduced gastric cancer risk in heterozygote model and dominant model whereas rs11614913 indicates no significant association. Subgroup analysis demonstrates that C allele of rs2910164 and rs11614913 may decrease susceptibility to diffuse type gastric cancer in dominant model and recessive model, respectively, while rs11614913 increased intestinal type gastric cancer in dominant model. Conclusion. SNPs rs2910164 and rs11614913 might have effect on gastric cancer risk in certain genetic models and specific types of cancer. Further well-designed studies should be considered to validate the potential effect.

Meta-analysis of the association between the rs7903146 polymorphism at the TCF7L2 locus and type 2 diabetes mellitus susceptibility.

Type 2 diabetes mellitus (T2DM) is a chronic disease caused by genetic and environmental factors. T2DM has been associated with specific polymorphisms in the TCF7L2 gene. This study evaluates the relationship between the rs7903146 locus polymorphism of the TCF7L2 gene and T2DM susceptibility through meta-analysis; the overall aim is to provide a basis for evidence-based medicinal treatment of T2DM. Cohort and case-control studies from Medline, PubMed, EMBASE, CBM, CNKI, and academic conferences/dissertations that examined the correlation between T2DM and rs7903146 polymorphisms were evaluated. We determined whether the TCF7L2 rs7903146 locus was associated with T2DM susceptibility by comparing alleles and genotypes. The Stata 11.0 software was applied for meta-analysis, and a random-effects model was adopted for heterogeneity testing and odds ratio (OR) calculation. A fixed-effect model was used for quantitative analysis of the heterogeneity between different studies, and for calculating the percentage of variability I(2). A total of 10 studies related to the rs7903146 loci and T2DM susceptibility were enrolled; this included 3404 cases of T2DM patients and 6473 control cases. Meta-analysis showed that the T allele of rs7903146 was significantly correlated with the risk of T2DM, with both a dominant fixed-effect model (OR = 1.653, 95%CI = 1.416-1.653) and a co-dominant-fixed effect model (OR = 1.525, 95%CI = 1.350-1.723). Meta-analysis revealed that the T allele of rs7903146 was also correlated with T2DM susceptibility.

Association study of polymorphisms in miRNAs with T2DM in Chinese population.

Accumulated evidence indicates that microRNA (miRNA or miR) is involved in the development of type 2 diabetes (T2DM). Several studies have shown that single nucleotide polymorphisms (SNPs) located in miRNAs are associated with T2DM in Caucasian populations. The association studies of miRNA's SNPs with T2DM in Asian are rarely reported, and there are distinct genetic differences between Caucasian and Asian populations. The focus of this study, therefore, is the association of T2DM with five SNPs (rs895819 in miR-27a, rs531564 in miR-124a, rs11888095 in miR-128a, rs3820455 in miR-194a and rs2910164 in miR-146a) located in five miRNAs in a Han Chinese population. A total of 738 subjects with T2DM and 610 non-diabetic subjects were genotyped using the TaqMan method. Next, the associations between the five SNPs with T2DM and individual metabolic traits were evaluated. Our data showed that the C allele of rs531564 in miR-124a may protect against T2DM (P=0.009, OR=0.758; 95%CI: 0.616-0.933). Conversely, the C allele of rs2910164 in miR-146a may increase the risk of developing T2DM (P<0.001, OR=1.459; 95%CI: 1.244-1.712). However, these five SNPs did not exhibit significant associations with individual metabolic traits in either the T2DM or non-diabetic groups. Our results revealed that genetic variations in miRNAs were associated with T2DM susceptibility in a Han Chinese population, and these results highlight the need to study the functional effects of these variants in miRNAs on the risk of developing T2DM.

A common polymorphism in pre-miR-146a underlies Hirschsprung disease risk in Han Chinese

BackgroundHirschsprung disease (HSCR) is a rare multigenic congenital disorder characterized by the absence of the enteric ganglia. To date, single nucleotide polymorphisms (SNPs) in pre-miRNAs have been confirmed related with some diseases. Thus, we hypothesized that pre-miRNA polymorphisms might contribute to HSCR susceptibility. We investigated whether rs2910164 and rs11614913 of pre-miR-146a and pre-miR-196a2, are associated with HSCR. MethodsPolymorphisms were genotyped using the Taqman method. Real-time PCR was used for detecting the expression level of miR-146a and its target gene ROBO1 in CC and GG genotypes. ResultsSignificant differences were found in the genotype distribution of rs2910164 and rs11614913 polymorphism between HSCR cases and controls (p=0.023 and 0.041, respectively). Furthermore, G allele of rs2910164 might increase the risk of HSCR (OR, 1.54; 95% CI, 1.06–2.23). Moreover, the expression level of miR-146a for homozygote GG was also higher than homozygote CC (p=0.0193). In contrast, the expression level of its target gene ROBO1 predicted in bioinformatics for homozygote GG was much lower than homozygote CC (p=0.0096). ConclusionsOur results showed that the polymorphism rs2910164 in pre-miR-146a might alter the production of mature miR-146a and then down-regulate the target gene ROBO1, which plays an important role in pathogenesis of HSCR.

Inverse association between obesity predisposing FTO genotype and completed suicide.

The A allele of rs9939609 in the FTO gene predisposes to increased body mass index (BMI) and obesity. Recently we showed an inverse association between the obesity related A allele of rs9939609 and alcohol dependence which was replicated by others. Since this finding raises a possibility that FTO may be associated with other psychiatric phenotypes, we aimed to examine association of rs9939609 with completed suicide. We genotyped rs9939609 in 912 suicide victims and 733 controls using TaqMan approach. We observed an inverse association between suicide and the rs9939609 A allele (OR = 0.80, P = 0.002, Pcor = 0.006) with genotype distribution suggesting a co-dominant effect. Given the link between alcoholism and suicide under influence of alcohol reported in Polish population, confounding by alcohol addiction was unlikely due to apparently similar effect size among cases who were under influence of ethanol at the time of death (OR = 0.76, P = 0.003, N = 361) and those who were not (OR = 0.80, P = 0.007, N = 469). The search for genotype-phenotype correlations did not show significant results. In conclusion, our study proves that there is an inverse association between rs9939609 polymorphism in FTO gene and completed suicide which is independent from association between FTO and alcohol addiction.

Correlation between TCF7L2 gene polymorphism and genetic susceptibility in women with gestational diabetes mellitus

To investigate the relationship between single nucleotide polymorphism (SNP) of transcription factor 7-like 2 (TCF7L2) at locus rs7903146, rs290487, rsl1196205, rs12255372 and genetic susceptibility in women with gestational diabetes mellitus (GDM). As a case- control study, 100 pregnant women with GDM and 100 healthy pregnant women in the Maternal and Children Health Hospital of Jiangxi Province were recruited from January 2010 to July 2013. Clinical parameters, including body mass index (BMI), fasting insulin (FINS), fasting plasma glucose (FPG) and homeostatic model assessment-insulin resistance index (HOMA-IR) were measured after admission to hospital. Allelespecific PCR was used to analyze the SNP of TCF7L2 at locus rs7903146, rs290487, rs11196205, rs12255372. (1)The BMI, FPG, FINS and HOMA-IR in GDM group were (27.4 ± 3.0)kg/m², (5.6 ± 1.0) mmol/L, (6.2 ± 3.4) mU/L and 1.8 ± 1.0, and were (24.2 ± 2.9) kg/m², (5.3 ± 0.8) mmol/L, (4.5 ± 2.8) mU/L, 1.2 ± 0.8 in the control group, respectively. The differences had statistically significance (P < 0.05). (2)The SNP of TCF7L2 gene, locus rs7903146 were CC, CT and TT genotype; the SNP of locus rs290487 were CC, CT and TT genotype; and the SNP of locus rs11196205 were GG and CC genotype; while the SNP of locus rs12255372 was GG genotype. (3) The distribution frequencies of genotype CC, CT and TT at locus rs7903146 in the GDM group were 40% (40/100), 36% (36/100) and 24% (24/100), respectively. While in the control group, they were 55% (55/100), 38% (38/100) and 7% (7/100), respectively. The frequencies of C and T allele of rs7903146 were 58%and 42% in the GDM group, and in the control group they were 74% (148/200) and 26% (52/200). The differences of genotype distribution and C/T allele frequency of rs7903146 between the two groups were statistically significant (P < 0.05). (4) The distribution frequencies of genotype CC, CT and TT at locus rs290487 in the GDM group were 12% (12/100), 36% (36/ 100) and 52% (52/100), and were 16% (16/100), 34% (34/100)and 50% (50/100) in the control group. The frequencies of C and T allele of rs290487 were 30% (60/200) and 70% (140/200) in the GDM group, and were 33% (66/200) and 67% (134/200) in the control group. There was no difference of genotype distribution and C/T allele frequency of rs290487 between the two groups (P > 0.05). (5)The distribution frequencies of genotype GG and CC at locus rs11196205 in the GDM group were 99% (99/100) and 1% (1/100), while those in the control group were 100% (100/100)and 0%. The frequency of G and C allele of rs11196205 were 99% (198/200) and 1% (2/200) in the GDM group, while in the control group were 100% (200/200) and 0. There was no difference of genotype distribution and G/C allele frequency of rs11196205 between the two groups (P > 0.05). (6)The distribution frequencies of genotype GG at locus rs12255372 were 100% (100/100) in both the GDM group and the control group. The frequencies of G allele of rs12255372 were 100% (200/200) in both the GDM group and the control group. There was no difference of genotype distribution and G allele frequency of rs12255372 between the two groups (P > 0.05). (7) After adjusting for age, gestational age, BMI, FPG and FINS, pregnant women with TT genotype at locus rs7903146 were more likely to have hyperglycemia compared with the C allele carriers (OR = 2.77, 95% CI: 1.03-7.57, P < 0.05). The polymorphism of locus rs7903146 in TCF7L2 gene may be associated with genetic susceptibility in women with GDM. TT genotype is likely to be risk factor in the pathogenesis of GDM.

MiR-146a and miR-196a2 polymorphisms in patients with ischemic stroke in the northern Chinese Han population.

MicroRNAs are endogenous non-coding RNAs about 22 nucleotides in length that can repress the expression of proteins by binding to the 3'-untranslated regions of target messenger RNAs. We hypothesized that polymorphisms in miR-146a and miR-196a2 are associated with risk of ischemic stroke in the northern Chinese Han population. In a case-control study of 368 ischemic stroke patients and 381 control subjects that were frequency matched by age and gender, we genotyped two single nucleotide polymorphisms (rs11614913 in miR-196a2 and rs2910164 in miR-146a) using polymerase chain reaction-ligation detection reaction. The frequencies of the rs2910164 CC genotype and C allele within miR-146a were not significantly different in patients with ischemic stroke compared with those in the healthy control group. In subgroup meta-analysis, rs2910164 in miR-146a and large-artery atherosclerosis, rather than small-vessel disease, showed the significant association under the dominant model (CC vs CG+GG, OR 1.694; 95 % CI 1.199-2.395 p = 0.003). After adjusting for confounding risk factors of ischemic stroke by logistic regression analysis, this significant correlation remained. In addition, the distributions of the miR-196a2 genotypes and alleles were not statistically different between ischemic stroke and healthy groups. We also did not find any significant association from stroke subtypes. The CC genotype and C allele of rs2910164 within miR-146a are associated with an increased incidence of large-artery atherosclerotic stroke in the northern Chinese Han population. This study indicates that miR-146a (rs2910164) might contribute to ischemic stroke susceptibility in the northern Chinese Han population.

Aspirin Use, 8q24 Single Nucleotide Polymorphism rs6983267, and Colorectal Cancer According to CTNNB1 Alterations

Regular aspirin use reduces the risk for colorectal cancer (CRC), possibly through inhibition of WNT/cadherin-associated protein β1 (CTNNB1 or β-catenin) signaling. The single nucleotide polymorphism (SNP) rs6983267 on chromosome 8q24 is a CRC susceptibility locus that affects binding activity of transcription factor 7 like-2 (TCF7L2) to CTNNB1, thereby altering expression of target oncogenes, including MYC. We evaluated regular aspirin use and CRC risk according to genotypes of SNP rs6983267 and CTNNB1 expression status in two prospective case-control studies (840 CRC case patients and 1686 age- and race-matched control subjects) nested within the Nurses' Health Study and the Health Professionals Follow-up Study. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) using unconditional logistic regression models. All statistical tests were two-sided. A lower risk of CRC was associated with regular aspirin use and the T allele of rs6983267. The effect of aspirin was confined to individuals with protective T allele of rs6983267 (additive matching factors-adjusted OR for T allele = 0.83; 95% CI = 0.74 to 0.94; P trend = .002; P interaction = .01). Additionally, the T allele of rs6983267 was associated with a reduced expression of MYC oncogene (P trend = .03). Moreover, among individuals with protective T allele, the effect of regular aspirin use was limited to those with positive nuclear CTNNB1 expression. In a functional analysis, in vitro treatment of LS174T cells (a cell line heterozygous for rs6983267) with aspirin was statistically significantly associated with higher G/T allelic ratio of TCF7L2 immunoprecipitated DNA (P = .03). Our results support an influence of aspirin on WNT/CTNNB1 signaling and suggest that aspirin chemoprevention may be tailored according to rs6983267 genotype.

A replication study examining association of rs6983267, rs10090154, and rs1447295 common single nucleotide polymorphisms in 8q24 region with prostate cancer in Siberians

IntroductionMultiple genetic studies have confirmed association of 8q24 variants with susceptibility to prostate cancer (CaP). However, the risk conferred in men living in Russia is unknown. Materials and methodsIn this work we studied the association of rs6983267, rs10090154, and rs1447295 single nucleotide polymorphisms (SNPs) with a risk of CaP development in men of Caucasoid descent living in the Siberian region of Russia. Three 8q24 SNPs were genotyped by real-time polymerase chain reaction in histologically confirmed CaP “cases” (n = 392) and clinically evaluated “controls” (n = 344). To evaluate the SNP effects on CaP susceptibility, odds ratio (OR) and confidence interval (CI) 95% were calculated. Allele and genotype frequencies in the groups were compared using logistic regression; differences were considered statistically significant if P<0.05. ResultsWe showed statistically significant association of the A allele of rs1447295 (OR [CI 95%] = 1.96 [1.37–2.81], P<0.0001) and the T allele of rs10090154 (OR [CI 95%] = 2.14 [1.41–3.26], P<0.0001) with CaP. The T-A rs10090154 to rs1447295 haplotype was also associated with CaP (OR [CI 95%] = 2.47 [1.59–3.85], P<0.0001). There was no significant association with the T allele of rs6983267: OR [CI 95%] = 0.9 [0.73–1.11], P> 0.05. ConclusionThus, our investigation confirms the role of chromosomal region 8q24 in the development of CaP in the Russian population.