目的:脂联素(ADIPOQ)基因被认为是破译2型糖尿病遗传基础的有前途的参与者之一。这项研究调查了ADIPOQ基因的三个单核苷酸多态性(SNPs)的单倍型组合和ADIPOQ受体基因的两个SNPs与环境危险因素之间的关系,以预测伊朗人群的T2DM疾病易感性。
方法:本病例对照和横断面研究对182例T2DM患者和155例健康对照进行。使用扩增难治性突变系统-PCR(ARMS-PCR)对rs17300539G/A进行基因分型,rs2241766T/G,和ADIPOQ基因的rs1501299G/T,AdipoR1基因的rs1342387C/T,和AdipoR2基因的rs10773989T/C。
结果:所有多态性均满足Hardy-Weinberg平衡(p>0.05)。研究的SNPs;ADIPOQ基因的rs17300539,rs2241766和AdipoR2基因的rs10773989,与T2DM风险增加显著相关。双向方差分析表明rs2241766T/G的GG携带者与TT携带者相比,腰臀比和体重指数明显降低,与任何其他基因型相比,rs2241766T/G的GG显示出最高的HbA1c水平。rs10773989T/C的CC携带者与其他两种基因型携带者相比显示出明显更高的LDL水平。根据组合单倍型([rs17300539,rs2241766,rs1501299]/[rs17300539,rs2241766,rs1501299])分析,GTT纯合子携带者显示出最高的血浆脂联素水平。相比之下,GGG/GTG,ATG/GTG,GGG/GGG在对照组中显示最低的血浆脂联素水平。
结论:脂联素基因单倍型组合与健康人血浆脂联素浓度相关。在T2DM中,脂联素遗传变异对血浆脂联素浓度的影响较小。
OBJECTIVE: Adiponectin (ADIPOQ) gene is considered to be one of the promising players in deciphering the genetic bases of type 2 diabetes. This study investigated the associations between
haplotype combinations of three single nucleotide polymorphisms (SNPs) of the ADIPOQ gene and two SNPs of the ADIPOQ receptor genes with environmental risk factors for the prediction of T2DM disorder susceptibility in the Iranian population.
METHODS: This case-control and cross-sectional study was conducted on 182 patients with T2DM and 155 healthy controls. Genotyping was performed using amplification refractory mutation system-PCR (ARMS-PCR) for rs17300539G/A, rs2241766T/G, and rs1501299G/T of the ADIPOQ gene, rs1342387C/T of the AdipoR1 gene, and rs10773989T/C of the AdipoR2 gene.
RESULTS: All polymorphisms met the Hardy-Weinberg equilibrium (p > 0.05). The studied SNPs; rs17300539, rs2241766 of ADIPOQ gene and rs10773989of AdipoR2 gene, were significantly associated with increased risk of T2DM. Two-way ANOVA analysis indicated that GG carriers of rs2241766T/G had a significantly lower waist-to-hip ratio and body mass index compared to TT carriers, and also GG of rs2241766T/G showed the greatest HbA1c levels compared to any other genotype. CC carriers of rs10773989T/C displayed a significantly higher LDL level compared to the other two genotype carries. According to Combined
Haplotype ([rs17300539, rs2241766, rs1501299] / [rs17300539, rs2241766, rs1501299]) analysis, GTT- homozygote carriers displayed the highest plasma adiponectin levels. In contrast, GGG/GTG, ATG/GTG, and GGG/GGG showed the lowest plasma adiponectin levels in the controls.
CONCLUSIONS: The adiponectin gene
haplotype combinations were associated with plasma adiponectin concentrations in healthy people. In T2DM, adiponectin genetic variants displayed less effect on adiponectin plasma concentrations.