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09-12-2010 | Diabetes | Article

Variation in WFS1 gene linked to increased risk for Type 2 diabetes


Free abstract

MedWire News: The major alleles of three variants in the Wolfram syndrome 1 gene (WFS1) are associated with an increased risk for Type 2 diabetes, report researchers from the DESIR study.

WFS1 was investigated for links with diabetes because mutations in this gene cause the rare Wolfram syndrome, which is characterized by diabetes, optical atrophy, and other endocrine and neurological abnormalities.

Gilberto Velho (INSERM, Paris, France) and colleagues genotyped 5110 French men and women who participated in the Data from Epidemiological Study on the Insulin Resistance Syndrome (DESIR) for three single nucleotide polymorphism (SNPs) in WFS1; rs10010131, rs1801213/rs7672995, and rs734312.

DESIR was a 9-year prospective study. At baseline, 88.9%, 6.6%, and 2.6%, of the participants had normal or impaired fasting glucose (IFG), or diabetes, respectively. The incidence of diabetes and hyperglycemic events in previously nondiabetic or IFG individuals during the study was 5.1% and 16.7%, respectively.

The incidence of Type 2 diabetes was found to be a significant 34% greater in carriers of the major G allele of rs10010131 than noncarriers, with a similar risk increase seen in carriers of the major G and A alleles of the SNPs rs1801213 and rs734312, respectively.

Carriers of the combined GGA haplotype for these SNPs had a 26% increased risk for developing diabetes compared with carriers of the ACG haplotype.

The researchers also note that there were significant associations between the three SNPs and plasma glucose, insulin, and glycated hemoglobin levels, both at baseline and throughout the study in those with diabetes or IFG at baseline.

Velho and team replicated the association between the major alleles of the three SNPs and diabetes in a cross sectional study of Type 2 diabetic and nondiabetic patients.

"Further studies with much larger sample sizes are required to identify the functional variants responsible for increased diabetes risk," conclude the authors in the journal Diabetologia.

MedWire ( is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

By Helen Albert