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

Objective: Group IVA cytosolic phospholipase A₂ (cPLA ₂α) 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 ₂ α gene polymorphisms and phenotypic features of patients with familial adenomatous polyposis (FAP). Patients and Methods: A tag single nucleotide polymorphisms (SNPs)-based genotype-phenotype association study of the cPLA ₂ α gene was conducted in 73 Japanese patients from 59 families with FAP. Based on the HapMap database, seven tag SNPs of the cPLA ₂ α 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. Results: 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). Conclusions: The cPLA ₂ α gene may be a possible disease modifier gene in FAP.