Impact of group IVA cytosolic phospholipase A2 gene polymorphisms on phenotypic features of patients with familial adenomatous polyposis
Impact of group IVA cytosolic phospholipase A2 gene polymorphisms on phenotypic features of patients with familial adenomatous polyposis
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DOI：
10.1007/s00384-009-0808-x
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发表时间：
2010-03
影响因子：
2.8
通讯作者：
J. Umeno;T. Matsumoto;M. Esaki;Yoji Kukita;T. Tahira;Ritsuko Yanaru-Fujisawa;Shotaro Nakamura;H. Arima;M. Hirahashi;K. Hayashi;M. Iida
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文献类型：
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作者：
J. Umeno;T. Matsumoto;M. Esaki;Yoji Kukita;T. Tahira;Ritsuko Yanaru-Fujisawa;Shotaro Nakamura;H. Arima;M. Hirahashi;K. Hayashi;M. Iida
ObjectiveGroup IVA 胞质磷脂酶 A2 (cPLA2α) 通过生成花生四烯酸作为环氧合酶的底物，在肿瘤发生中发挥关键作用。本研究的目的是阐明 cPLA2α 基因多态性与家族性腺瘤性息肉病 (FAP) 患者表型特征之间可能的关联。 患者和方法 对来自 59 个 FAP 家族的 73 名日本患者进行了基于标签单核苷酸多态性 (SNP) 的 cPLA2α 基因基因型-表型关联研究。基于HapMap数据库，选择cPLA2α基因的7个标签SNP，通过直接测序分析进行基因分型。还评估了与腺瘤性息肉病大肠杆菌 (APC) 基因突变相关的基因型-表型关联。结果单个 SNP 分析显示 rs3820185 C 等位基因 [比值比 (OR), 2.5; 比值比 (OR), 2.5; 95%置信区间（CI），1.2-4.9]和rs127446200 GG基因型（OR，10.9；95%CI，1.6-69.8）在胃底腺息肉病（FGP）患者中比没有胃底腺息肉病的患者更常见。 Rs12749354 C 等位基因在小肠腺瘤患者中更常见（OR，7.0；95% CI，1.5–30.4；p= 0.008）。在逻辑回归分析中调整协变量（年龄、性别和 APC 突变）时，这种关联也很显着（调整后 OR，7.4；95% CI，1.2–64.2；p= 0.027）。结论 ThecPLA2α 基因可能是 FAP 中可能的疾病调节基因。
ObjectiveGroup 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 betweencPLA2α gene polymorphisms and phenotypic features of patients with familial adenomatous polyposis (FAP).Patients and MethodsA tag single nucleotide polymorphisms (SNPs)-based genotype–phenotype association study of thecPLA2α gene was conducted in 73 Japanese patients from 59 families with FAP. Based on the HapMap database, seven tag SNPs of thecPLA2α gene were selected and genotyped by direct sequencing analysis. The genotype–phenotype association in relation to theadenomatous polyposis coli(APC) gene mutation was also assessed.ResultsThe 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, andAPCmutation) in a logistic regression analysis (adjusted OR, 7.4; 95% CI, 1.2–64.2;p= 0.027).ConclusionsThecPLA2α gene may be a possible disease modifier gene in FAP.