Identification of the G994T polymorphism in exon 9 of plasma platelet-activating factor acetylhydrolase gene as a risk factor for polycystic ovary syndrome.

Abstract

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

The G994T polymorphism in PAFAH gene may be one of the genetic determinants for PCOS in Chinese Han women.

• Authors: Ping Fan, Hong-Wei Liu, Xiao-Su Wang, Feng Zhang, Qi Song, Qin Li, Hong-Mei Wu, Huai Bai
• Journal: Human reproduction (Oxford, England) (Hum Reprod) Vol. 25 Issue 5 Pg. 1288-94 (May 2010) ISSN: 1460-2350 [Electronic] England
• PMID: 20185515 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA Primers
• 1-Alkyl-2-acetylglycerophosphocholine Esterase

Topics

• 1-Alkyl-2-acetylglycerophosphocholine Esterase (blood, genetics)
• Adolescent
• Adult
• Alleles
• Asian People (genetics)
• Base Sequence
• Case-Control Studies
• China
• DNA Primers (genetics)
• Exons
• Female
• Gene Frequency
• Humans
• Polycystic Ovary Syndrome (enzymology, genetics)
• Polymorphism, Single Nucleotide
• Risk Factors
• Young Adult