Laboratory of Genetic Disease and Perinatal Medicine, West China Second University Hospital, Sichuan University, Chengdu 610041, Sichuan, People's Republic of China.
Hum Reprod. 2010 May;25(5):1288-94. doi: 10.1093/humrep/deq047. Epub 2010 Feb 25.
Low-grade chronic inflammation and greater risks of cardiovascular diseases are often present in patients with polycystic ovary syndrome (PCOS). Platelet-activating factor (PAF) acetylhydrolase (PAF-AH) hydrolyzes and inactivates PAF and PAF-like oxidized phospholipids that are potent lipid mediators involved in inflammation and atherosclerosis. Deficiency of this enzyme is caused by a missense mutation (G994 --> T) in exon 9 of the plasma PAF-AH gene. The aim of the study was to investigate a possible association of this polymorphism with the risk of PCOS and to evaluate the effects of the genotype on the activity and distribution of PAFAH in Chinese patients.
A total of 661 subjects (346 patients with PCOS and 315 healthy control women) from a population of Chinese Han nationality in Chengdu area were included in this study. PAFAH G994T genotype was studied using PCR and restriction fragment length polymorphism analysis. Total plasma PAF-AH, high-density lipoprotein (HDL)-associated PAF-AH (H-PAF-AH) and low-density lipoprotein (LDL)-associated PAF-AH (L-PAF-AH) activities were measured by the trichloroacetic acid precipitation procedure using [(3)H-acetyl] PAF and PAF C-16 as a substrate.
The prevalence of the mutant genotype (GT + TT) was significantly more frequent in patients with PCOS than in control subjects (12.7 versus 6.0%, P = 0.003). Genotype (GT + TT) remained a significant predictor for PCOS (P = 0.020) in prognostic models including age, body mass index, insulin resistance index, triglyceride, HDL and LDL as covariates. There was a significant difference in plasma PAF-AH, L-PAF-AH and H-PAF-AH activities between GG and GT genotypes in both the patient and control groups. The ratio of L-PAF-AH to H-PAF-AH activities was significantly higher after adjustment for multiple variables in patients with GT genotype compared with patients with GG genotype (P = 0.003). There were no significant differences in clinical, biochemical and metabolic parameters according to PAFAH G994T genotyping in patients with PCOS and control women.
The G994T polymorphism in PAFAH gene may be one of the genetic determinants for PCOS in Chinese Han women.
多囊卵巢综合征（PCOS）患者常伴有低度慢性炎症和更高的心血管疾病风险。血小板激活因子（PAF）乙酰水解酶（PAF-AH）可水解失活 PAF 和 PAF 样氧化磷脂，这些物质是参与炎症和动脉粥样硬化的强效脂质介质。该酶的缺乏是由于血浆 PAF-AH 基因外显子 9 中的错义突变（G994→T）引起的。本研究旨在探讨该多态性与 PCOS 发病风险的可能相关性，并评估基因型对中国患者 PAF-AH 活性和分布的影响。
本研究纳入了来自成都地区汉族人群的 661 例受试者（346 例 PCOS 患者和 315 例健康对照女性）。采用 PCR 和限制性片段长度多态性分析研究 PAFAH G994T 基因型。采用三氯乙酸沉淀法，以[(3)H-乙酰] PAF 和 PAF C-16 为底物，测定总血浆 PAF-AH、高密度脂蛋白（HDL）相关 PAF-AH（H-PAF-AH）和低密度脂蛋白（LDL）相关 PAF-AH（L-PAF-AH）活性。
PCOS 患者中突变基因型（GT+TT）的发生率明显高于对照组（12.7%比 6.0%，P=0.003）。在包括年龄、体重指数、胰岛素抵抗指数、甘油三酯、HDL 和 LDL 在内的协变量的预后模型中，基因型（GT+TT）仍然是 PCOS 的显著预测因素（P=0.020）。在患者组和对照组中，GG 和 GT 基因型之间的血浆 PAF-AH、L-PAF-AH 和 H-PAF-AH 活性均存在显著差异。GT 基因型患者 L-PAF-AH 与 H-PAF-AH 活性的比值在调整多个变量后明显高于 GG 基因型患者（P=0.003）。PCOS 患者和对照组女性根据 PAFAH G994T 基因分型在临床、生化和代谢参数方面无显著差异。
PAFAH 基因 G994T 多态性可能是中国汉族女性 PCOS 的遗传决定因素之一。
