Impact of group IVA cytosolic phospholipase A2 gene polymorphisms on phenotypic features of patients with familial adenomatous polyposis.
OBJECTIVE
Group IVA cytosolic phospholipase A(2) (cPLA(2)alpha) 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 )alpha gene polymorphisms and phenotypic features of patients with familial adenomatous polyposis (FAP).


METHODS
A tag single nucleotide polymorphisms (SNPs)-based genotype-phenotype association study of the cPLA ( 2 )alpha gene was conducted in 73 Japanese patients from 59 families with FAP. Based on the HapMap database, seven tag SNPs of the cPLA ( 2 )alpha 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 )alpha gene may be a possible disease modifier gene in FAP.
Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka, 812-8582, Japan. jumeno@intmed2.med.kyushu-u.ac.jp
Junji
J
Umeno
Takayuki
T
Matsumoto
Motohiro
M
Esaki
Yoji
Y
Kukita
Tomoko
T
Tahira
Ritsuko
R
Yanaru-Fujisawa
Shotaro
S
Nakamura
Hisatomi
H
Arima
Minako
M
Hirahashi
Kenshi
K
Hayashi
Mitsuo
M
Iida
D011125:Adenomatous Polyposis Coli / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D002648:Child; D005260:Female; D020022:Genetic Predisposition to Disease; D054513:Group IV Phospholipases A2 / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D055815:Young Adult
D025601:Adenomatous Polyposis Coli Protein; D054513:Group IV Phospholipases A2; C516389:PLA2G4A protein, human