Effect of the R92H and A379V genotypes of platelet-activating factor acetylhydrolase on its enzyme activity, oxidative stress and metabolic profile in Chinese women with polycystic ovary syndrome.
BACKGROUND
The 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.


METHODS
A 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.


RESULTS
No 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.


CONCLUSIONS
There 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.
Laboratory of Genetic Disease and Perinatal Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, 610041, People's Republic of China.
Renjiao
R
Zhang
Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, 610041, People's Republic of China.
Qi
Q
Song
Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, 610041, People's Republic of China.
Hongwei
H
Liu
Laboratory of Genetic Disease and Perinatal Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, 610041, People's Republic of China.
Huai
H
Bai
Laboratory of Genetic Disease and Perinatal Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, 610041, People's Republic of China.
Yujin
Y
Zhang
Laboratory of Genetic Disease and Perinatal Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, 610041, People's Republic of China.
Qingqing
Q
Liu
Laboratory of Genetic Disease and Perinatal Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, 610041, People's Republic of China.
Linbo
L
Guan
Laboratory of Genetic Disease and Perinatal Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, 610041, People's Republic of China. fanping15@scu.edu.cn.
Ping
P
Fan
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000235:genetics* / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D053299:Apolipoprotein B-100 / Q000097:blood; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D018384:Oxidative Stress / Q000235:genetics*; D011085:Polycystic Ovary Syndrome / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic; D055815:Young Adult
C569471:APOB protein, human; D053299:Apolipoprotein B-100; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; C526684:PLA2G7 protein, human
Enzyme activity; Gene polymorphism; Oxidative stress; PAF acetylhydrolase; Polycystic ovary syndrome