Male preponderance in early diagnosed type 2 diabetes is associated with the ARE insertion/deletion polymorphism in the <it>PPP1R3A </it>locus

Abstract

Abstract Background The ARE insertion/deletion polymorphism of PPP1R3A has been associated with variation in glycaemic parameters and prevalence of diabetes. We have investigated its role in age of diagnosis, body weight and glycaemic control in 1,950 individuals with type 2 diabetes in Tayside, Scotland, and compared the ARE2 allele frequencies with 1,014 local schoolchildren. Results Men homozygous for the rarer allele (ARE2) were younger at diagnosis than ARE1 homozygotes (p = 0.008). Conversely, women ARE2 homozygotes were diagnosed later than ARE1 homozygotes (p = 0.036). Thus, men possessing the rarer (ARE2) allele were diagnosed with type 2 diabetes earlier than women (p Comparison of the male to female ratios at different ages-diagnosed confirms a known phenomenon that men are much more prone to early type 2 diabetes than women. When this feature was examined by the common ARE 1/1 genotype we found that the male to female ratio remained at unity with all ages of diagnosis, however, carriers of the ARE2 variant displayed a marked preponderance of early male diagnosis (p = 0.003). Conclusion The ARE2 allele of PPP1R3A is associated with a male preponderance to early diagnosed type 2 diabetes. Susceptibility to type 2 diabetes in later life is not modulated by the ARE2 allele in either sex.