Genetic Variation Of SNP-43 In Calpain-10 Gene Is Not A Major Factor In The Occurrence Of Type 2 Diabetes And Insulin Resistance In Chinese

Linkage studies in Mexican-American affected sib pairs living in Starr County localized a major susceptibility locus for type 2 diabetes,NIDDM1,to chromosome band 2q37.3[1]. This susceptibility locus, NIDDM1,originally encompassed perhaps 10-20cM,but the target region was subsequently narrowed to 7 cM by COX et al[2]. Horikawa et al[3] sequenced approximately 66kb in this region,revealing two genes and one expressed sequence tag.One gene.designated calpain-10.encodes a new member of the cysteine protease family,and the other encodes G protein-coupled receptor 35; SNP-43 in intron 3 of calpain-10 showed an increase in the frequence of the common G allele in patients compared with controls.and this SNP was also associated with evidence for linkage.Evans et al[4] suggested that calpain-10 may increase T2DM risk in white subjects of English/Irish ancestry, Horikawa et al[5],Fingerlin et al[6] suggested that calpain-10 SNP-43 is not a major factor in the occurrence of type 2 diabetes in Japanese and Finnish. We typed SNP-43 in the calpain-10 gene to test for association between genetic variation of SNP-43 at these loci and type 2 diabetes and insulin resistance in 316 Chinese Han subjects of Dalian.Method A total of 316 unrelated Chinese patients of Dalian were randomly selected in our in-patient department.119 T2DM(According to WHO 1999 criteria[10], 76 men and 43 women) ,the average age of the T2DM patients was 56.49 ± 12.32 years and the average BMI was 24.21±2.61 kg/m2; the average age of the 197 non-diabetes normal controls(without T2DM family history, 116men and 81 women) was 56.68± 15.29 years, the average BMI was 23.31 ±2.00 kg/m2.197 non-diabetes normal controls(without T2DM family history) were selected, fasting plasma glucose and fasting plasma insulin were measured. SNP-43 was genotyped with PCR and RFLP methods. The frequencies of SNP-43 genotype and allele gene were compared betweensubjects with T2DM and those with NFPG;In NFPG group, the frequencies of SNP-43 genotype and allele gene were also compared between subgroups consisted of subjects with SNP-43GG with BMI ≥ 25kg/m2,SNP-43GG with BMI < 25kg/m2,SNP-43 GA+AA with BMI≥25kg/m2 and SNP-43 GA+AA with BMK25kg/m2 respectively. NFPG subjects were divided into two groups(SNP-43GG group and SNP-43 GA+AA group),then compare the differences of the value of FPG,FINS,HOMA-IR and HOMA-B cell index; NFPG subjects were also divided into four groups(SNP-43GG group with BMI≥25kg/m2,SNP-43GG group with BMI<25kg/m2,SNP-43 GA+AA group with BMI≥25kg/m2 and SNP-43 GA+AA group with BMI<25kg/m2),then compare the differences of the value of FPG,FINS ,HOMA-IR and HOMA- P cell index.Result The frequencies of GG, GA and AA genotypes of CAPN-10 SNP-43 were 0.868, 0.122 and 0.010 respectively ; SNP-43 has allelic frequencies of G-0.93 and A=0.07 in Han people of Dalain Chinese. The frequencies of SNP-43 genotype and allele gene were not differed between subjects with T2DM and those with NFPG; the frequencies of SNP-43 genotype and allele gene were not differed between SNP-43GG group with BMI≥25kg/m2,SNP-43GG group with BMI<25kg/m2,SNP-43 GA+AA group with BMI≥25kg/m2 and SNP-43 GA+AA group with BMI<25kg/m2.In NFPG subjects.the value of FPG,FINS,HOMA-IR and HOMA- P cell index were not differed between subjects with SNP-43GG and those with non- SNP-43GG; the value of FPG,FINS,HOMA-IR and HOMA- P cell index were not differed between SNP-43GG group with BMI≥25kg/m2,SNP-43GG group with BMI<25kg/m2,SNP-43 GA+AA group with BMI≥25kg/m2 and SNP-43 GA+AA group with BMI<25kg/m2.Conclusion The CAPN10 SNP-43 is not related to type 2 diabetes and insulin resistance in Han people of northern Chinese.