Naturally occurring mutations in the melanocortin receptor 3 gene are not associated with type 2 diabetes mellitus in French Caucasians

Familial genetic studies of type 2 diabetes (T2DM) of different human popul ations, including the French Caucasians, suggested evidence for Linkage of T2DM and human chromosome 20q13, a region where maps the melanocortin 3 rec eptor gene (MC3R). Likewise, its homologous MC4R in human obesity, MC3R gen e is also a good candidate for genetic susceptibility to glucose intoleranc e and T2DM. We therefore undertook a molecular study to assess the role of genetic variations of this gene in a large cohort of French families with T 2DM. In these patients, we identified two missense mutations in the MC3R ge ne: Val(81)Ile and Lys(6)Thr. These two variants, which were in complete li nkage disequilibrium, were also present in nondiabetic controls. Based on a ssociation and familial linkage disequilibrium tests results, we found that these MC3R gene-coding variants were not associated with diabetes or obesi ty. These variants were found, however, marginally associated with insulin and glucose levels during oral glucose tolerance testing in normoglycemic s ubjects. Overall, the present study provides no evidence for a major role o f the MC3R coding mutations underlying the genetic linkages of T2DM and the MC3R gene region on chromosome 20q13 in T2DM families from France and othe r geographical origins.