Dataset Information

Association between STAT4 gene polymorphism and type 2 diabetes risk in Chinese Han population.

ABSTRACT:

Background

Evidence from genetic epidemiology indicates that type 2 diabetes (T2D) has a strong genetic basis. Activated STAT4 has an inflammatory effect, and STAT4 is an important mediator of inflammation in diabetes. Our study aimed to study the association between STAT4 single nucleotide polymorphisms (SNPs) and T2D susceptibility in Chinese Han population.

Methods

We conducted a 'case-control' study among 500 T2D patients and 501 healthy individuals. 5 candidate STAT4 SNPs were successfully genotyped. The association between SNPs and T2D susceptibility under different genetic models was evaluated by logistic regression analysis. 'SNP-SNP' interaction was analyzed and completed by multi-factor dimensionality reduction (MDR). Finally, we evaluated the differences of clinical characteristics under different genotypes by one-factor analysis of variance.

Results

The overall results showed that STAT4 rs3821236 was associated with increasing T2D risk under allele (OR 1.23, p = 0.020), homozygous (OR 1.51, p = 0.025), dominant (OR 1.36, p = 0.029), and additive models (OR 1.23, p = 0.020). The results of stratified analysis showed that rs3821236, rs11893432, and rs11889341 were risk factors for T2D among participants ≤ 60 years old. Only rs11893432 was associated with increased T2D risk among female participants. There was also a potential association between rs3821236 and T2D with nephropathy risk. STAT4 rs11893432, rs7574865 and rs897200 were significantly associated with lysophosphatidic acid, cystatin C and thyroxine t4, respectively.

Conclusion

The genetic polymorphisms of STAT4 is potentially associated with T2D susceptibility of Chinese population. In particular, rs3821236 is significantly associated with T2D risk both in the overall and several subgroup analyses. Our study may provide new ideas for T2D individualized diagnosis/protection.

SUBMITTER: Cui J

PROVIDER: S-EPMC8237503 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundAccumulating evidences have shown that miRNAs are directly or indirectly involved in a variety of biological processes, and closely associated with diverse human diseases, including cardiovascular diseases. SNPs locating within pri/pre-miRNA can affect miRNA processing and binding ability of target genes. MiR-27a, miR-26a-1 miR-100, miR-126 and miR-218 were reported to be associated with pathogenesis of myocardial infarction (MI). Here we aimed to evaluate the potential association of five polymorphisms in these pri/pre-miRNAs with individual susceptibility to MI in a Chinese Han population.MethodsGenotyping was performed in 287 MI cases and 646 control subjects using polymerase chain reaction-ligase detection reaction (PCR-LDR) method. The association of these SNPs with MI risk was performed with SPSS software.ResultsIn a logistic regression analysis, we found that AG heterozygote (OR = 0.40, 95% CI = 0.21-0.76, Pa = 0.005) or AA homozygote (OR = 0.40, 95% CI = 0.22-0.75, Pa = 0.004) of pre-miR-27a rs895819 had a reduced susceptibility to MI in comparison with GG homozygote. Similarly, a reduced risk of MI was detected when the AG and AA genotypes were combined (OR = 0.40, 95% CI = 0.22-0.74, Pa = 0.003). However, no significant association between pri-miR-26a-1 pri-miR-100, pri-miR-126 and pri-miR-218 polymorphisms and MI risk was observed under the allelic and established genetic models. Further stratified analysis of pre-miR-27a rs895819 revealed a more significant association of AG + AA genotypes with MI risk among younger, male and smoking subjects. Interestingly, AG and AA genotypes of the rs895819 polymorphism conferred about 0.17 mmol/L and 0.18 mmol/L increase in HDL-C levels compared to GG genotype.ConclusionsOur findings suggest that the pre-miR-27a rs895819 polymorphism is associated with MI susceptibility in the Chinese Han population, which probably due to influence the HDL-C levels.