Impact of group IVA cytosolic phospholipase A 2 gene polymorphisms on phenotypic features of patients with familial adenomatous polyposis.

Group IVA cytosolic phospholipase A2 (cPLA2α) plays a key role in tumorigenesis via generating arachidonic acids as the substrate of cyclooxygenase. The aim of this study was to elucidate the possible associations between cPLA 2α gene polymorphisms and phenotypic features of patients with familial adenomatous polyposis (FAP). A tag single nucleotide polymorphisms (SNPs)-based genotype–phenotype association study of the cPLA 2α gene was conducted in 73 Japanese patients from 59 families with FAP. Based on the HapMap database, seven tag SNPs of the cPLA 2α gene were selected and genotyped by direct sequencing analysis. The genotype–phenotype association in relation to the adenomatous polyposis coli ( APC) gene mutation was also assessed. The single SNP analysis showed that rs3820185 C allele [odds ratio (OR), 2.5; 95% confidence interval (CI), 1.2–4.9] and rs127446200 GG genotype (OR, 10.9; 95%CI, 1.6–69.8), were more frequent in patients with gastric fundic gland polyposis (FGP) than in those without. Rs12749354 C allele was more frequently found in patients with small intestinal adenoma (OR, 7.0; 95% CI, 1.5–30.4; p = 0.008). This association was also significant when adjusted for covariates (age, sex, and APC mutation) in a logistic regression analysis (adjusted OR, 7.4; 95% CI, 1.2–64.2; p = 0.027). The cPLA 2α gene may be a possible disease modifier gene in FAP. [ABSTRACT FROM AUTHOR]