Abstract
BackgroundThe G994T polymorphism in platelet-activating factor acetylhydrolase (PAF-AH) gene is associated with the risk of polycystic ovary syndrome (PCOS). The aim of this study was to investigate the relationship between R92H and A379V variants of the PAF-AH gene and the risk of PCOS and to evaluate the effects of the genotypes on PAF-AH activities and clinical, metabolic and oxidative stress indexes in Chinese women.MethodsA total of 862 patients with PCOS based on the Rotterdam consensus criteria and 750 control women from a population of Chinese Han nationality in the Chengdu area were studied from 2006–2015. PAF-AH genotypes were determined by PCR and restriction fragment length polymorphism analysis. Plasma PAF-AH, high-density lipoprotein (HDL)-associated PAF-AH (H-PAF-AH) and apolipoprotein (apo) B-containing lipoprotein-associated PAF-AH (apoB-PAF-AH) activities were measured using the trichloroacetic acid precipitation procedure with PAF C-16 as a substrate. Circulating markers of oxidative stress, including serum total oxidant status, total antioxidant capacity, oxidative stress index and malondialdehyde levels, and clinical and metabolic parameters were also analyzed.ResultsNo significant differences were observed in the frequencies of R92H and A379V genotypes and alleles of the PAF-AH gene between PCOS and control groups (P > 0.05). Compared with patients with the 92RR genotype, patients with H allele of R92H (RH + HH genotype) had significantly higher plasma PAF-AH and apoB-PAF-AH activities (P < 0.05) and tended to exhibit increased H-PAF-AH activity (P = 0.063) after adjusted for age and BMI. However, when serum LDL-C, HDL-C, TG and HOMA index were added as covariates, the comparisons no longer remained statistical significance (P > 0.05). There were no significant differences in clinical, hormonal, metabolic and circulating oxidative stress parameters and the frequencies of PAF-AH G449T genotype according to PAF-AH R92H or A379V genotyping in patients with PCOS and control women.ConclusionsThere were no significant associations between R92H and A379V variants of PAF-AH gene and risk of PCOS in Chinese women. The increased plasma PAF-AH and apoB-PAF-AH activities in patients with H allele of R92H are related to the R92 → H variation, changes in plasma lipoprotein levels, insulin resistance, aging, and gaining weight and thus may be involved in the pathogenesis of PCOS and the increased risks of future cardiovascular diseases.
Highlights
The G994T polymorphism in platelet-activating factor acetylhydrolase (PAF-AH) gene is associated with the risk of polycystic ovary syndrome (PCOS)
TT and luteinizing hormone (LH) levels, the ratio of LH to follicle stimulating hormone (FSH), fasting insulin concentration, HOMA index, TG, total cholesterol (TC), low-density lipoprotein (LDL)-C, apolipoprotein B (apoB) and MDA levels, total oxidant status (TOS), total antioxidant capacity (T-AOC), oxidative stress index (OSI), the ratio of apoBPAF-AH to H-PAF-AH and the frequency of the T allele carriers (GT + TT) of PAF-AH G994T were significantly increased and FSH and high-density lipoprotein (HDL)-C levels and H-PAF-AH activities were significantly reduced in the PCOS group compared with the control group after adjusted for age and body mass index (BMI) (Table 2)
When serum LDL cholesterol (LDL-C), HDLC, TG and HOMA index were added as covariates, the comparisons of plasma PAF-AH, apoB-PAF-AH and H-PAF-AH activities as well as the ratio of apoB-PAFAH to H-PAF-AH were statistically significant (P < 0.05)
Summary
The G994T polymorphism in platelet-activating factor acetylhydrolase (PAF-AH) gene is associated with the risk of polycystic ovary syndrome (PCOS). In addition to reproductive disorders, PCOS is often associated with long-term health risks, including insulin resistance, obesity, dyslipidemia, increased oxidative stress, chronic low-grade inflammation, endothelial dysfunction and vascular injury, elevated risks of metabolic syndrome, type 2 diabetes, and future cardiovascular diseases [2,3,4,5,6,7,8,9]. Decreased HDL-associated PAF-AH (H-PAF-AH) activities, increased apoB-containing lipoprotein-associated PAF-AH (apoB-PAF-AH) activities and/or the ratio of apoB-PAFAH to total or H-PAF-AH activity are associated with cardiovascular diseases [14], type 2 diabetes [17], gestational diabetes mellitus [13], pre-eclampsia [18], and polycystic ovary syndrome [19, 20] and might be markers for chronic inflammation in these patients
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