Type 2 diabetes and three Calpain-10 gene polymorphisms in Samoans: No evidence of association

Although genomewide scans have identified several potential chromosomal sus ceptibility regions in several human populations, finding a causative gene for type 2 diabetes has remained elusive. Others have reported a novel gene , calpain-10 (CAPN10), located in a previously identified region on chromos ome 2q37.3, as a putative susceptibility gene for type 2 diabetes. Three si ngle-nucleotide polymorphisms (SNPs) (UCSNP43, UCSNP19, and UCSNP63) were s hown to be involved in increased risk of the disease among Mexican American s. We have tested the association of these three SNPs with type 2 diabetes among the Samoans of Polynesia, who have a very high prevalence of the dise ase. In the U.S. territory of American Samoa, prevalence is 25% and 15% in men and women, respectively, whereas, in the independent nation of Samoa, p revalence is 3% and 5% in men and women, respectively. In our study sample, which consisted of 172 unrelated affected case subjects and 96 control sub jects, we failed to detect any association between case subjects and contro l subjects in allele frequencies, haplotype frequencies, or haplotype combi nations of UCSNP43, -19, and -63. Also, our data showed no evidence of link age, among 201 affected sib pairs, in the region of chromosome 2 that conta ins these SNPs. Three plausible scenarios could explain these observations. (1) CAPN10 is a susceptibility gene only in particular ethnic groups; (2) our study lacks power to detect the effects of CAPN10 polymorphisms (but ou r sample size is comparable to that of earlier reports); or (3) the underly ing biological mechanism is too complex and requires further research.