Although genomewide scans have identified several potential chromosomal susceptibility 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 chromosome 2q37.3, as a putative susceptibility gene for type 2 diabetes. Three single-nucleotide polymorphisms (SNPs) (UCSNP43, UCSNP19, and UCSNP63) were shown to be involved in increased risk of the disease among Mexican Americans. 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 disease. 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, prevalence is 3% and 5% in men and women, respectively. In our study sample, which consisted of 172 unrelated affected case subjects and 96 control subjects, we failed to detect any association between case subjects and control subjects in allele frequencies, haplotype frequencies, or haplotype combinations of UCSNP43, -19, and -63. Also, our data showed no evidence of linkage, among 201 affected sib pairs, in the region of chromosome 2 that contains 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 our sample size is comparable to that of earlier reports); or (3) the underlying biological mechanism is too complex and requires further research.
Background and Purpose-The Phosphodiesterase 4D (PDE4D) gene was reported recently to be associated with ischemic stroke in an Icelandic population. The association was found predominately with large vessel and cardioembolic stroke. However, 2 recent reports were unable to confirm this association, although a trend toward association with cardioembolic stroke was reported. None of the reports included significant proportions of blacks. We tested for genotype and haplotype association of polymorphisms of the PDE4D gene with ischemic stroke in a population-based, biracial, case-control study. Methods-A total of 357 cases of ischemic stroke and 482 stroke-free controls from the same community were examined.Single nucleotide polymorphisms (SNPs) were chosen based on significant associations reported previously. Linkage disequilibrium (LD), SNP, and haplotype association analysis was performed using PHASE 2.0 and Haploview 3.2. Results-Although several univariate associations were identified, only 1 SNP (rs2910829) was found to be significantly associated with cardioembolic stroke among both whites and blacks. The rs152312 SNP was associated with cardioembolic stroke among whites after multiple comparison corrections. The same SNP was not associated with cardioembolic stroke among blacks. However, significant haplotype association was identified for both whites and blacks for all ischemic stroke, cardioembolic stroke, and stroke of unknown origin. Haplotype association was identified for small vessel stroke among whites. Conclusions-PDE4D is a risk factor for ischemic stroke and, in particular, for cardioembolic stroke, among whites and blacks. Further study of this gene is warranted. (Stroke. 2006;37:371-376.)
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