Mutations in the insulin promoter factor-1 gene in late-onset type 2 diabetes mellitus

Insulin promoter factor-1 (IPF-1) is a transcription factor expressed in pancreatic beta cells. Following the identification of missense variants in the coding regions of the IPF-1 gene, in subjects selected for a strong family history of type 2 diabetes, the aim of our study was to evaluate the prevalence of these variants in the common form of type 2 diabetes.

Three variants (C18R, Q59L and D76N) were screened by PCR-RFLP in a group of 296 unrelated French late-onset type 2 diabetic subjects consecutively recruited in a diabetes department of a university hospital, regardless of family history of diabetes.

The C18R and Q59L variants were each found in 0.37% of the diabetic patients, and in none of 147 controls. We did not detect the D76N variant, which was the most frequent variant in subjects with a strong family history of diabetes, in patients or controls.

We have observed a combined prevalence of missense variants in the coding region of the IPF-1 gene of around 1%, in unselected patients with the common form of late-onset type 2 diabetes. The prevalence of these variants in subjects with a strong family history of type 2 diabetes had been found to be as high as approximately 6%. These differences in prevalence might be related to differences in the clinical profile of patients, such as age of onset of diabetes and associated obesity, as well as a family history of diabetes.