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

作者：Cheurfa N; Brenner G M; Reis A F; Dubois Laforgue D; Roussel R; Tichet J; Lantieri O; Balkau B; Fumeron F; Timsit J; Marre M; Velho G^*

来源：Diabetologia, 2011, 54(3): 554-562.

DOI：10.1007/s00125-010-1989-0

• Endoplasmic reticulum stress
• Genetic epidemiology
• Population studies
• Wolframin

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.

• 出版日期2011-3