The 3 '-untranslated region polymorphism of the gene for skeletal muscle-specific glycogen-targeting subunit of protein phosphatase 1 in the type 2 diabetic Japanese population

A newly identified 3'-untranslated region (UTR) polymorphism of the gene fo r skeletal muscle-specific glycogen-targeting subunit of protein phosphatas e 1 (PPPIR3) was associated with insulin resistance and type 2 diabetes in Pima Indians (Xia J, Scherers W Cohen PTW Majer M, Xi T, Norman RA, Knowler WC, Bogardus C, Prochazka M: A common variant in PP1R3 associated with ins ulin resistance and type 2 diabetes. Diabetes 47:1519-1524, 1998). Thus, we investigated the frequency of polymorphism of the adenine- and thymine-ric h element (ARE-1 and its variant ARE-2) in 426 Japanese type 2 diabetic and 380 nondiabetic subjects using a polymerase chain reaction (PCR)restrictio n enzyme fragment length polymorphism (RFLP) method. The allele frequency o f the ARE-2 variant in diabetic subjects was higher than that in nondiabeti c subjects (0.34 vs. 0.29; P < 0.05), even though its frequency in Japanese subjects was lower (P < 0.001) than the reported value in Pima Indians (0. 56). An aspartate polymorphism at codon 905 was 100% coupled to the ARE-S a llele, and its allele frequency was higher also in diabetic subjects. Altho ugh a serine substitution at codon 883 was partially linked with the ARE-8 allele, there was no difference between diabetic and nondiabetic subjects. These results indicate that the frequency of polymorphism of the PPPIR3 gen e (ARE-S and Asp905) is different between two ethnic groups and is increase d in Japanese people with type 2 diabetes, suggesting that these variants m ay be a possible marker for searching for diabetogenic genes.