scholarly journals Effects of Genetic Variants of Nuclear Receptor Y on the Risk of Type 2 Diabetes Mellitus

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Ying Wang ◽  
Shanshan Yang ◽  
Qiuyue Guan ◽  
Jinglu Chen ◽  
Xueping Zhang ◽  
...  

Nuclear factor-Y (NF-Y) consists of three evolutionary conserved subunits including NF-YA, NF-YB, and NF-YC; it is a critical transcriptional regulator of lipid and glucose metabolism and adipokine biosynthesis that are associated with type 2 diabetes mellitus (T2DM) occurrence, while the impacts of genetic variants in the NF-Y gene on the risk of T2DM remain to be investigated. In the present study, we screened five single-nucleotide polymorphisms (SNPs) with the SNaPshot method in 427 patients with T2DM and 408 healthy individuals. Subsequently, we analyzed the relationships between genotypes and haplotypes constructed from these SNPs with T2DM under diverse genetic models. Furthermore, we investigated the allele effects on the quantitative metabolic traits. Of the five tagSNPs, we found that three SNPs (rs2268188, rs6918969, and rs28869187) exhibited nominal significant differences in allelic or genotypic frequency between patients with T2DM and healthy individuals. The minor alleles G, C, and C at rs2268188, rs6918969, and rs28869187, respectively, conferred a higher T2DM risk under a dominant genetic model, and the carriers of these risk alleles (either homozygotes of the minor allele or heterozygotes) had statistically higher levels of fasting plasma glucose, cholesterol, and triglycerides. Haplotype analysis showed that SNPs rs2268188, rs6918969, rs28869187, and rs35105472 formed a haplotype block, and haplotype TTAC was protective against T2DM (OR=0.76, 95% CI=0.33-0.82, P=0.004), while haplotype GCCG was associated with an elevated susceptibility to T2DM (OR=2.33, 95% CI=1.43-3.57, P=0.001). This study is the first ever observation to our knowledge that indicates the genetic variants of NF-YA might influence a Chinese Han individual’s occurrence of T2DM.

2018 ◽  
Vol 65 (3) ◽  
Author(s):  
Elena Kazakova ◽  
Meijun Chen ◽  
Esma Jamaspishvili ◽  
Zhang Lin ◽  
Jingling Yu ◽  
...  

Two recent studies found that RBMS1 gene rs7593730 and BCAR1 gene rs7202877 had relationships with type 2 diabetes. However, the association of these loci with type 2 diabetes mellitus (T2DM) has not been examined in Chinese. We performed a replication study to investigate the association of 2 susceptibility loci with T2DM in the Chinese population. We genotyped 1961 Chinese participants (991 with T2DM and 970controls) for each of the 2 single nucleotide polymorphisms (SNPs) rs7593730 in RBMS1 and rs7202877 near BCAR1 using SNPscan and examined the association of them with T2DM using logistic regression analysis. We also analyzed the correlation of the SNP allele and clinical phenotypes. In additive model, genotype association analysis of BCAR1 rs7202877 loci revealed that the homozygous of rs7202877 GG carriers had a significant decreased T2DM risk compared to homozygous carriers of TT (p= 0.038, OR 0.44, 95 % CI 0.20-0.96). In the recessive model, the genotype GG carriers had a significant decreased T2DM risk compared to GT+TT (p= 0.043, OR 0.67, 95% CI 0.46-0.99). Allele G was statistically significantly correlated with TC (mmol/L) (P=0.036) and LDL-C (mmol/L) (P=0.007). As for rs7593730, the carriers of genotype CT and TT had significantly decreased T2DM risk compared with the carriers of genotype CC (CT: CC P=0.038, OR 0.71, 95%CI 0.51-0.98; TT: CC P=0.010, OR 0.32, 95%CI 0.13-0.76). In a dominant model, TT+CT: CC (p= 0.013, OR 0.673, 95 % CI 0.49-0.92) and in a recessive model, TT: CT+CC (p= 0.019, OR 0.59, 95% CI 0.39-0.92). The T allele carriers had a significant decreased T2DM risk compared to carriers of C (p= 0.002, OR 0.65, 95 % CI 0.50-0.86). Allele T was statistically correlated with FINS (P=0.010). In conclusion, our study showed that RBMS1 gene rs7593730 and BCAR1 gene rs7202877 were significantly associated with type 2 diabetes in the Chinese population.


2019 ◽  
Vol 39 (8) ◽  
Author(s):  
Fangxiao Cheng ◽  
Lu Liu ◽  
Hongli Zhang ◽  
Yi Zhu ◽  
Xiaohua Li ◽  
...  

Abstract Objective: The aim of the present study was to explore the genetic association of single nucleotide polymorphisms (SNPs) in interleukin-16 (IL-16) gene with type 2 diabetes mellitus (T2DM) susceptibility in a Chinese Han population. Methods: In total, 133 T2DM patients and 127 healthy controls matched by age and gender were recruited in the case–control study. IL-16 gene rs4778889 and rs11556218 polymorphisms were genotyped in the two groups via polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Differences in genotype and allele distributions between groups were compared by the χ2 test. All the comparisons were adjusted for age, gender, and body mass index (BMI) by logistic regression. The odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the association strength between IL-16 gene polymorphism and T2DM risk. Results: The TG genotype and G allele frequencies of rs11556218 increased remarkably in the case group than that in controls (45.86 vs 33.86%; 29.70 vs 20.87%), and the differences reached a significant level (P<0.05). After adjusting for age, gender, and BMI, the differences still reached a significant level (P<0.05). Rs11556218 TG genotype carriers had a 1.769-fold increased risk of developing T2DM (OR = 1.769, 95% CI = 1.045–2.994), and G allele was also associated with an increased risk of T2DM (OR = 1.639, 95% CI = 1.087–2.471). IL-16 rs4778889 polymorphism showed no significant association with T2DM risk. Conclusion: IL-16 gene rs11556218 polymorphism was significantly associated with T2DM susceptibility in the Chinese Han population, while rs4778889 was not.


2020 ◽  
Author(s):  
Li Jin ◽  
Yan Huang ◽  
Yangyang Li ◽  
Bo Xu ◽  
Cheng Hu ◽  
...  

Abstract Background: CYP2C8 and CYP2C9 are cytochrome P450 epoxygenases that metabolize arachidonic acid into epoxyeicosatrienoic acids (EETs). EETs are important lipid mediators with many beneficial effects in type 2 diabetes mellitus. In this study, we aimed to investigate the association of CYP2C8 and CYP2C9 variants with type 2 diabetes in a Chinese population. Methods: We genotyped 9 tag single nucleotide polymorphisms (SNPs) in CYP2C8 and 10 tag SNPs in CYP2C9 based on HapMap Chinese and Japanese data. Then, we genotyped the SNPs in a Chinese population that included 3410 type 2 diabetes patients and 3401 normal controls. The association between the SNPs and type 2 diabetes was analysed. Results: In the study population, we found that rs1819173 in the CYP2C9 gene region was associated with type 2 diabetes and the A allele was protective against type 2 diabetes (odds ratio: 0.840, 95% confidence interval (CI): 0.780-0.904, P=3.04×10-6). Haplotypes GT and AT (rs2071426-rs6583967) in CYP2C8 were associated with type 2 diabetes (P=0.049 and 0.038, respectively). On the other hand, an interaction effect between rs1819173 in CYP2C9 and rs12766752 in CYP2C8 on type 2 diabetes was found (P=0.003). What’s more, rs1819173 showed significant association with HDL-C (high-density lipoprotein cholesterol).Conclusions: Our results suggested that common SNPs in the CYP2C8 and CYP2C9 regions were associated with T2DM in a Chinese Han population.


2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Wen-Jia Han ◽  
Jian-Yi Deng ◽  
Hua Jin ◽  
Li-Ping Yin ◽  
Jin-Xia Yang ◽  
...  

Background. Type 2 diabetes mellitus (T2DM) is one of the most common chronic diseases in adults, causing high morbidity and mortality worldwide. In recent years, the prevalence of T2DM has been increasing significantly, and genome-wide association studies (GWAS) have shown that KCNQ1 significantly increases the risk of T2DM. Objective. To find large-scale evidence on whether the KCNQ1rs2237892C⟶T gene polymorphism is associated with T2DM susceptibility. Methods. A comprehensive review of the Chinese and English literature on the association of T2DM with KCNQ1rs2237892 is published by PubMed and Baidu Academic. The included literature was part or all of the studied loci which were evaluated for association with T2DM. Forest plots were made of the included literature to analyze the association of KCNQ1 with polymorphisms of the studied loci, and funnel plots and Egger’s test were used to evaluate the publication bias of the selected included literature. Results. Ten case-control studies including a total of 7027 cases and 8208 controls met our inclusion criteria. Allele (C allele frequency distribution) (OR: 1.19; 95% CI: 0.87,1.62; P < 0.00001 ), recessive (OR: 0.73; 95% CI: 0.45,1.18; P < 0.00001 ) genetic model under the full population was observed between KCNQ1rs2237892C⟶T gene polymorphism and T2DM without a significant relationship. In a stratified analysis by race, a meaningful association was found in non-Asian populations under the allelic genetic model, but no association was found in Asian populations. Conclusion. This meta-analysis showed no significant association between the rs2237892 polymorphism of the KCNQ1 gene and the risk of T2DM.


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