A novel haplotyoe combination(111/121) in calpain-10 gene is significantly associated with Type 2 diabets in Korean

초록

Background and aims: Genetic Variation in CAPN 10, the gene encoding the cysteine protease calpan-10, has been associated with type 2 diabetes mellitus (T2 DM) in Mexican-Americans and two northern-Europeans (Finland and Germany). Nevertheless the other populations including Japanese showed variation of CAPN 10 does not strongly associated with T2 DM. Materials and methods: We replicated to genotype 3 SNPs in CAPN 10 defined a diabetes high-risk haplotype in Mexican Americans: UCSNP-43, -19, and 63. A total of 454 Korean patients with T2 DM (M/F, 230/222; age, 53.3?1.0 yr; BMI 24.4?.5; HbA1c, 8.4?.3) and a total of 236 nondiabetic Koreans (M/F, 124/112; age, 62.6?.1 yr; BMI 23.8?.7) with no family history of diabetes. The genomic DNA was isolated and 3 SNPs were examined by the electrophoresis of the PCR product by size or after digested with enzymes (Nsi I and Hha I). Results: There was no significant association with diabetes in 3 SNPs: UCSNP-43 (allele 1, G; 2, A; p=0.402), UCSNP-19 (allele 1, 2 repeat of 32 bp; allele 2, 3 repeat; p=0.153; in genotypic distribution, x2=3.37, p=0.07), and UCSNP-63 (allele 1, C; 2, T; p=0.326). The haplotype allelic distributions with PHASE program were 8 alleles (121, 122, 111, 112, 221, and 3 rare alleles) and showed significant association with T2 DM ( x2=18.78, p=0.001). After adjusted with sex and age, haplotype-allele 111 showed high risk of T2 DM (OR=2.23, p=0.001). And in the haplotype combinations, the haplotypes, 111/121 and 112/112, showed high risk of T2 DM (OR=3.34, p=0.001, and OR=2.38, p=0.049 respectively). The high-risk haplotype (112/121) in Mexican Americans was not significant (p=0.815). And especially in the obese subgroup (BMI>24.4), the haplotype 111/121 showed more increased risk of T2 DM (OR=4.29, p=0.004), comparing with less obese (BMI < 24.4, OR=2.94, p=0.005).