Opposite genetic effects of CMIP polymorphisms on the risk of type 2 diabetes and obesity: A family-based study in China

C-Maf Inducing Protein (CMIP) gene polymorphisms were reported to be associated with type 2 diabetes mellitus (T2DM). Whether the association between CMIP and T2DM is mediated via obesity-related phenotypes is still unclear. We analyzed the association of CMIP rs2925979 with T2DM and a comprehensive set of obesity-related phenotypes in 1576 families ascertained from a Chinese population. These families included a total of 3444 siblings (1582 with T2DM, 963 with prediabetes, and 899 with a normal glucose level). Using multi-level mixed effects regression models, we found that each copy of CMIP rs2925979_T allele was associated with a 29% higher risk of T2DM in females (p = 9.30 × 10⁻⁴), while it was not significantly associated with T2DM in males (p = 0.705). Meanwhile, rs2925979_T allele was associated with lower levels of body mass index (BMI), waist circumference (WC), hip circumference (HC), percentage of body fat (PBF), PBF of arms, PBF of legs, and PBF of trunk in nondiabetes females (all p < 0.05). The opposite associations of rs2925979_T allele with T2DM and obesity-related phenotypes suggest that CMIP may exert independent pleiotropic effects on T2DM and obesity-related phenotypes in females.