Mice lacking the integrin alphaMbeta2 (Mac-1, CD11b/CD18) develop an obese phenotype on western diet rich in fat. However, no association has been found between variations in the human genes encoding the integrin alphaMbeta2 and obesity. This study was aimed to investigate the association between a single-nucleotide polymorphism (SNP) (rs235326) in the gene encoding human integrin beta2 subunit (ITGB2) with obesity. Our subject cohort comprised 651 people of Japanese ethnicity, of which 274 were Japanese Americans living in Hawaii, and the remaining 377 were native Japanese, two populations in the same genetic background with or without westernized life style. We genotyped the rs235326 polymorphism using a TaqMan assay. In the Japanese-American population, the risk of obesity was found to be 3.29-fold higher (a 95% confidence interval of 1.25-8.67, P = 0.02) in TT homozygotes than in C carriers, using a recessive model and logistic regression analysis that had been adjusted for age. This association was not found in native Japanese individuals. These results indicate that the rs235326 polymorphism in the ITGB2 gene is associated with obesity in Japanese living in the United States whose diet has become "westernized."