Evidence for association between paraoxonase 1 gene polymorphisms and polycystic ovarian syndrome in south-west Chinese women

Abstract

Objective: The aim of this study was to investigate the relationship between 192Q/R and 55L/M polymorphisms of paraoxonase 1 (PON1) gene and polycystic ovarian syndrome (PCOS) in Chinese women. Design: A case-control study. Methods: A total of 1113 subjects (610 patients with PCOS and 503 control women) from a population of Chinese Han nationality in Chengdu area were included in this study. PON1 genotypes were studied using PCR and restriction fragment length polymorphism analysis. Clinical and metabolic parameters were analyzed. Results: The frequencies of PON1 192RR genotype and R allele were significantly higher in patients with PCOS than in control women (44.6 vs 36.4%, 0.667 vs 0.610 respectively). The 192RR genotype remained a significant predictor for PCOS (odds ratio RR/QRCQQ : 1.656, 95% confidence interval: 1.156-2.371) in prognostic models including age, body mass index, insulin resistance index, triglyceride, HDL, and LDL as covariates. Compared with patients with QQ genotype, patients with RR or QR genotype had significantly higher waist circumference and fasting insulin and triglyceride levels, patients with RR genotype had significantly higher waist-to-hip ratio, and patients with QR genotype had significantly higher homeostasis model assessment of insulin resistance. Such relationships were not detected in the control women. No significant differences were found in the frequencies of PON1 55L/M genotype and allele between PCOS and control groups. Conclusions: The 192Q/R, but not 55L/M, polymorphism in PON1 gene is associated with the risk of PCOS in south-west Chinese women.

Lactonase activity and status of paraoxonase 1 in Chinese women with polycystic ovarian syndrome

“…Consistent with our results, the PON1 genetic polymorphisms have been shown to regulate the PON1 status on HDL in circulation and account for more than 60% of the interindividual variation in enzyme concentration and activity (12,13,34). Studies have found that the promoter region K108C/T variants decrease the PON1 expression and protein level, the PON1 Q192R polymorphism itself does not affect PON1 protein concentrations but greatly influences the PON1 activities, and the PON1 55L/M polymorphism influences both the PON1 concentrations and activities (12,55).…”

“…On the other hand, we also found that unlike the control 192QR or RR genotypic subgroups, the increase in PON1 lactonase activities and NLA is of limited in PCOS patients with 192QR or RR genotype (Table 3). Our previous study showed that the PCOS patients with QR or RR genotype had significantly higher or tend to increase WC, WHR, fasting insulin and TG levels, and HOMA-IR compared with patients with QQ genotype, while such relationships were not detected in the control women (34), suggesting that abdominal obesity and insulin resistance, which is often associated with the decreased apoA1 levels and the increased plasma glucose levels, may impair PON1 lactonase activities by the glycation of HDL and the reduced stimulation of apoA1 on PON1 (13). In addition, we found that the PON1 concentrations were lowest and the degree of catalytic stimulation by HDL was highest in the subjects harboring the 55LM genotype.…”

“…In addition, unlike most other studies, we find that the PON1 concentrations were higher in the controls harboring the PON1 192RR genotype than in controls harboring the QQ or QR genotype. The increases may be due to the PON1 K108C allele, which increases PON1 expression and may partly compensate for the PON1 concentrations afforded by the R isoform because the PON1 192R allele has been reported to be in linkage disequilibrium with the PON1 K108C allele (34,56). Similarly, the effects of PON1 55L/M polymorphism on the PON1 concentrations and activities might be largely due to the linkage disequilibrium among the 55L, 192R, and K108C alleles and between 55M and 192Q (34,56).…”

“…HA was assessed as total testosterone (TT) levels above the 95th percentile of the levels (2.60 nmol/l) detected in a group of normal menstruating women with normal cycles and/or clinically by the presence of obvious acne (33) and/or hirsutism with a F-G score of more than 6 (33,34,35). PCO was confirmed if 12 or more follicles in each ovary measured 2-9 mm in diameter and/or the ovarian volume was increased (O10 ml) by ultrasonic examination with exclusion of other etiologies, such as congenital adrenal hyperplasia, androgen-secreting carcinomas, and Cushing's syndrome.…”

“…The genomic DNA was isolated from the peripheral blood leukocytes of subjects and the PON1 K108C/T, 192Q/R, and 55L/M genotypes were assessed by PCR amplification and restriction analysis as described previously (34,37).…”