Decreased insulin secretion and increased risk of type 2 diabetes associated with allelic variations of the WFS1 gene: the Data from Epidemiological Study on the Insulin Resistance Syndrome (DESIR) prospective study
Decreased insulin secretion and increased risk of type 2 diabetes associated with allelic variations of the WFS1 gene: the Data from Epidemiological Study on the Insulin Resistance Syndrome (DESIR) prospective study
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DOI：
10.1007/s00125-010-1989-0
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发表时间：
2011-03-01
期刊：
影响因子：
8.2
通讯作者：
Velho, G.
中科院分区：
文献类型：
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作者：
Cheurfa, N.;Brenner, G. M.;Velho, G.
我们在一项普通人群前瞻性研究中调查了WFS 1基因等位基因变异与胰岛素分泌和2型糖尿病风险的关系，我们研究了5，110名无血缘关系的法国男性和女性，他们参加了胰岛素抵抗综合征流行病学研究（ENUR）的前瞻性数据研究。对4,472名法国2型糖尿病患者和3,065名对照者进行了额外的横断面分析。对3个单核苷酸多态性（SNPs）进行基因分型：rs 10010131、rs 1801213/rs7672995和rs734312。我们观察到这3个变异的主要等位基因与基线时BXR队列中的2型糖尿病患病率之间存在统计学显著相关性。考克斯分析显示rs 10010131的G-等位基因与2型糖尿病发病之间存在关联（HR 1.34，95% CI 1.08-1.70，p = 0.007）。对于rs 1801213的G-等位基因和rs734312的A-等位基因观察到类似的结果。与ACG单倍型相比，GGA单倍型与糖尿病风险增加相关（HR 1.26，95% CI 1.04-1.42，p = 0.02）。我们还观察到，在2型糖尿病或有糖尿病风险的个体中，这三种SNP与基线时和整个研究期间的血糖、HbA（1c）水平和胰岛素分泌之间存在统计学显著相关性。然而，在随访结束时血药浓度正常的患者中未观察到相关性。在2型糖尿病患者与非糖尿病对照组的横断面研究中，重复了这三个变异体与2型糖尿病之间的关联，在包含WFS 1基因的单倍型块中最常见的单倍型调节胰岛素分泌，并与2型糖尿病风险增加相关。
We investigated associations of allelic variations in the WFS1 gene with insulin secretion and risk of type 2 diabetes in a general population prospective study.We studied 5,110 unrelated French men and women who participated in the prospective Data from Epidemiological Study on the Insulin Resistance Syndrome (DESIR) study. Additional cross-sectional analyses were performed on 4,472 French individuals with type 2 diabetes and 3,065 controls. Three single nucleotide polymorphisms (SNPs) were genotyped: rs10010131, rs1801213/rs7672995 and rs734312.We observed statistically significant associations between the major alleles of the three variants and prevalent type 2 diabetes in the DESIR cohort at baseline. Cox analyses showed an association between the G-allele of rs10010131 and incident type 2 diabetes (HR 1.34, 95% CI 1.08-1.70, p = 0.007). Similar results were observed for the G-allele of rs1801213 and the A-allele of rs734312. The GGA haplotype was associated with an increased risk of diabetes as compared with the ACG haplotype (HR 1.26, 95% CI 1.04-1.42, p = 0.02). We also observed statistically significant associations of the three SNPs with plasma glucose, HbA(1c) levels and insulin secretion at baseline and throughout the study in individuals with type 2 diabetes or at risk of developing diabetes. However, no association was observed in those who remained normoglycaemic at the end of the follow-up. Associations between the three variants and type 2 diabetes were replicated in cross-sectional studies of type 2 diabetic patients in comparison with a non-diabetic control group.The most frequent haplotype at the haplotype block containing the WFS1 gene modulated insulin secretion and was associated with an increased risk of type 2 diabetes.