A Leu184Val polymorphism in PCK1 gene is associated with type 2 diabetes in Eastern Chinese population with BMI<23 kg/m2.

Our previous finding has shown that a suggestive linkage existed in D20S196 in diabetic families with lowered BMI in eastern Chinese population. The aim of this study is to investigate whether variants in PCK1 gene, located in this region, was associated with type 2 diabetes in eastern China. Eleven SNPs were identified by sequencing in PCK1. The G (Val184) allele of rs707555 (Leu184Val) in diabetic group was associated with type 2 diabetes (P=0.015; odds ratio 1.42 [95% CI 1.08-1.88]), and was much stronger in subgroup with the BMI<23kg/m(2) (P=0.008). rs2070755, located in intron 4, was also associated with type 2 diabetes (P=0.037; odds ratio 1.29 [95% CI 1.03-1.64]), especially in subgroup with the BMI<23 kg/m(2) (P=0.018). The enzymatic activity of PEPCK-C containing Leu184 was higher than that of PEPCK-C containing Val184 (P<0.01). These results showed that Val184 of PCK1 gene might increase the risk of type 2 diabetes in eastern Chinese population with BMI<23 kg/m(2) via reducing the PEPCK-C activity.