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ADRA2A rs553668 变异与 2 型糖尿病相关,在一项来自墨西哥城的基于人群的病例对照研究中,有五个变异与该疾病在名义显著水平相关。

The ADRA2A rs553668 variant is associated with type 2 diabetes and five variants were associated at nominal significance levels in a population-based case-control study from Mexico City.

机构信息

Department of Genetics and Molecular Biology, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV), Mexico City, Mexico.

Department of Genetics and Molecular Biology, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV), Mexico City, Mexico.

出版信息

Gene. 2018 Aug 30;669:28-34. doi: 10.1016/j.gene.2018.05.078. Epub 2018 May 22.

Abstract

Type 2 diabetes (T2D) is a disease with a prevalence of 9.4% in Mexicans. Its etiology is complex involving environmental and genetic factors. The aim of this study was to analyse the association between PPARG rs1801282, PPARGC1A rs8192678, VEGFA rs2010963, ADRA2A rs553668, KCNQ1 rs2237892, SIRT1 rs7896005, IGF2BP2 rs4402960, and UCP3 rs3781907 single nucleotide variants (SNVs) with T2D and metabolic traits in a case-control study of a population from Mexico City. A total of 831 blood samples of non-diabetic, with healthy control participants (416) and individuals with T2D (415) were collected over a five-year period. After DNA extraction, genotyping was performed with TaqMan probes using real-time PCR. The genotypes were analysed for association with T2D in linear and logistic regressions adjusting for age, sex, and body mass index using the dominant, recessive, and additive models with a Bonferroni correction for multiple comparisons p < 0.001 and for association with related T2D traits fixed with a p < 2.3 × 10. The univariate analysis gives a significant (p < 1 × 10) for sex, triglycerides, and HOMA-IR. Significant association with T2D was found for ADRA2A rs553668 under the recessive model (OR = 3.640 and 95% CI of 2.330-5.690 (p < 1 × 10); statistical power 0.999) and under the additive model (OR = 1.640 and 95% CI of 1.340-2.000 (p < 1 × 10); statistical power 0.997). Variants PPARG rs1801282, PPARGC1A rs8192678, SIRT1 rs7896005, IGF2BP2 rs4402960 and UCP3 rs3781907 were nominally associated (p > 0.001 and <0.050). Results describe association of ADRA2A rs553668 with T2D in a Mexican population. Variants with nominal association with T2D require to be replicated in additional Mexican populations.

摘要

2 型糖尿病(T2D)在墨西哥的患病率为 9.4%。其病因复杂,涉及环境和遗传因素。本研究旨在分析 PPARG rs1801282、PPARGC1A rs8192678、VEGFA rs2010963、ADRA2A rs553668、KCNQ1 rs2237892、SIRT1 rs7896005、IGF2BP2 rs4402960 和 UCP3 rs3781907 单核苷酸变异(SNVs)与 T2D 及代谢特征之间的关联,这是一项在墨西哥城人群中进行的病例对照研究。在五年的时间里,共采集了 831 份非糖尿病、健康对照组(416 人)和 T2D 患者(415 人)的血样。提取 DNA 后,使用 TaqMan 探针通过实时 PCR 进行基因分型。使用线性和逻辑回归分析,在调整年龄、性别和体重指数后,采用显性、隐性和加性模型进行基因型与 T2D 的关联分析,多重比较的 Bonferroni 校正 p 值<0.001,与相关的 T2D 特征的关联固定为 p 值<2.3×10。单变量分析表明性别、甘油三酯和 HOMA-IR 有显著差异(p<1×10)。ADRA2A rs553668 在隐性模型下(OR=3.640,95%CI 为 2.330-5.690(p<1×10);统计功效 0.999)和加性模型下(OR=1.640,95%CI 为 1.340-2.000(p<1×10);统计功效 0.997)与 T2D 有显著关联。PPARG rs1801282、PPARGC1A rs8192678、SIRT1 rs7896005、IGF2BP2 rs4402960 和 UCP3 rs3781907 变体呈名义关联(p>0.001 且<0.050)。结果描述了 ADRA2A rs553668 与墨西哥人群 T2D 的关联。与 T2D 具有名义关联的变体需要在其他墨西哥人群中进行复制。

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