Linkage and association studies have detected a role for Calpain-10 (CAPN10) polymorphisms in susceptibility to T2DM in many populations. This study aimed to evaluate possible associations between three SNPs in the CAPN10 (UCSNPs -43, -19 and -63) gene and T2DM in the east Indian population. The distribution of genotype frequency of UCSNP-63 varied significantly between T2DM patients and controls under a dominant model. The uncommon (T) allele (OR = 3.74, 95% CI: 1.44-9.7) of the UCSNP-63 and haplotype 112 (OR = 3.4, 95% CI: 1.17-9.9) were associated with increased risk of T2DM. On the contrary, the most common haplotype 121 (OR = 0.70 95% CI: 0.50-0.99) was associated with a reduced risk for T2DM. In our population a novel 111/112-haplotype combination created by the CAPN10 UCSNP-43, -19 and —63 was associated with risk of T2DM. Haplotypes 112 and 121 with opposite genetic influences also co-exist in our population.
DeFronzo RA, Bonadonna RC, Ferrannini E. ( 1992) Pathogenesis of NIDDM: A balanced overview. Diabetes Care15: 318-368.
2.
Wild S., Roglic G., Green A., Sicree R., King H. ( 2004) Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care27: 1047-1053.
3.
Cassell PG, Jackson AE, North BV, et al. (002) Haplotype combinations of Calpain 10 gene polymorphisms associate with increased risk of impaired glucose tolerance and type 2 diabetes in South Indians. Diabetes51: 1622-1628.
4.
Poulsen P., Andersen G., Fenger M., et al. (2003) Impact of two common polymorphisms in the PPARγ gene on glucose tolerance and plasma insulin profiles in monozygotic and dizygotic twins. Diabetes52: 194-198.
5.
Gloyn AL, Weedon MN, Owen KR, et al. (2003) Large-scale association studies of variants in genes encoding the pancreatic ß-cell KATP channel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) confirm that the KCNJ11 E23K variant is associated with type 2 diabetes. Diabetes52: 568-572.
6.
Yamagata K., Furuta H., Oda N., et al. (1996) Mutations in the hepatocyte nuclear factor- 4α gene in the maturity onset diabetes of the young (MODY). Nature384: 458-460.
7.
Kunika K., Tanahashi T., Numata S., et al. (2008) Common coding variant in the TCF7L2 gene and study of the association with type 2 diabetes in Japanese subjects. J Hum Genet53: 972-982.
8.
Tabassum R., Chavali S., Dwivedi OP, Tandon N., Bharadwaj D. ( 2008) FOXA2 variants may affect risk of type 2 diabetes and metabolic traits in North India: Genetic variants of FOXA2: risk of type 2 diabetes and effect on metabolic traits in North Indians. J Hum Genet53: 957-965.
9.
Sanghera DK, Ortega L., Han S., et al. (2008) Impact of nine common type 2 diabetes risk polymorphisms in Asian Indian Sikhs: PPARG2 (Pro12Ala), IGF2BP2, TCF7L2 and FTO variants confer a significant risk. BMC Med Genet9: 59.
10.
Singh PP, Naz I., Gilmour A., Singh M., Mastana S. ( 2006) Association of APOE (Hha1) and ACE (I/D) gene polymorphisms with type 2 diabetes mellitus in North West India. Diabetes Res Clin Pract74: 95-102.
11.
Bid HK, Konwar R., Agrawal CG, Banerjee M. ( 2008) Association of IL-4 and IL-1RN (receptor antagonist) gene variants and the risk of type 2 diabetes mellitus: A study in the north Indian population. Indian J Med Sci62: 259-266.
12.
Horikawa Y. , Oda N., Cox NJ, et al. (2000) Genetic variation in the gene encoding Calpain 10 is associated with type 2 diabetes mellitus . Nat Genet26: 163-175.
13.
Evans JC, Frayling TM, Cassell PG, et al. (2001) Variation in the calpain 10 gene and type 2 diabetes: studies of association between the gene for calpain-10 and type 2 diabetes mellitus in the United Kingdom. Am J Hum Genet69: 544-552.
14.
Barrett JC, Fry B., Maller J., Daly MJ ( 2005) Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics21: 263-265.
15.
Malecki MT, Moczulski DK, Klupa T., et al. (2002) Homozygous combination of Calpain-10 gene haplotypes is associated with type 2 diabetes mellitus in a Polish population . Eur J Endocrinol146: 695-699.
16.
Kang ES, Kim HJ, Nam Mncm, Cha Cwabs, Lee HC ( 2006) A novel 111/121 diplotype in the Calpain-10 gene is associated with type 2 diabetes. J Hum Genet51: 629-633.
17.
Elbein SC, Chu W., Ren Q., et al. (2002) Role of calpain-10 gene variants in familial type 2 diabetes in Caucasians. J Clin Endocrinol Metab87: 650-654.
18.
Iwasaki N., Horikawa Y., Tsuchiya T., et al. (2005) Genetic variants in the calpain-10 gene and the development of type 2 diabetes in the Japanese population. J Hum Genet50: 92-98.
19.
King H., Aubert RE, Herman WH ( 1998) Global burden of diabetes 1995-2025; Prevalence, numerical estimates, and projection. Diabetes Care21: 1414-1431.
20.
Saha A., Adak S., Chowdhury S., Bhattacharyya M. ( 2005) Enhanced oxygen releasing capacity and oxidative stress in diabetes mellitus and diabetes mellitus-associated cardiovascular disease: a comparative study. Clin Chimi Acta361: 141-149.
