Yujin Zhang1, Hongwei Liu1, Jin He1, Kelei Xu1, Huai Bai1, Ying Wang1, Feng Zhang1, Jinxia Zhang1, Li Cheng1, Ping Fan2. 1. Department of Obstetrics and GynecologyWest China Second University HospitalWest China School of PharmacyLaboratory of Genetic Disease and Perinatal Medicine and Key Laboratory of Birth Defects and Related Diseases of Women and Children of Ministry of EducationWest China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, People's Republic of China. 2. Department of Obstetrics and GynecologyWest China Second University HospitalWest China School of PharmacyLaboratory of Genetic Disease and Perinatal Medicine and Key Laboratory of Birth Defects and Related Diseases of Women and Children of Ministry of EducationWest China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, People's Republic of China fanping15@scu.edu.cn.
Abstract
OBJECTIVE: To study the relationship between the lactonase activities and status of paraoxonase 1 (PON1) and its association with the PON1 genetic polymorphisms in women with polycystic ovarian syndrome (PCOS). DESIGN: A case-control study. METHODS: A total of 455 PCOS patients and 441 control women were included in this study. The lactonase activities and concentrations of PON1 were assayed using 5-thiobutyl butyrolactone (TBBL) and 7-O-diethylphosphoryl-3-cyano-4-methyl-7-hydroxycoumarin (DEPCyMC) respectively. A normalized lactonase activity (NLA) was estimated based on the ratio of TBBLase:DEPCyMCase activity. The PON1 genotypes, serum malondialdehyde (MDA) levels and total antioxidant capacity were analyzed. RESULTS: The lactonase activities and levels of PON1 were higher in PCOS patients than in the control women. However, the NLA did not significantly differ between groups. The -108C→T variation of the PON1 gene showed decreased lactonase activities and levels of PON1 in a genotype-dependent manner (CC>CT>TT); the 192Q→R variation of the PON1 gene showed increased PON1 lactonase activities and NLA; and the 55L→M variation of the PON1 gene showed decreased lactonase activities and levels of PON1 but an increased NLA. A multivariable regression analysis showed that the -108C/T, 192Q/R, and 55L/M variations of the PON1 gene, serum apolipoprotein A1, and MDA levels were significant predictors of PON1 lactonase activity, PON1 level, and NLA. CONCLUSIONS: The serum lactonase activities and concentrations of PON1 are increased in PCOS patients. The increased oxidative stress and the -108C/T, 192Q/R, and 55L/M genetic polymorphisms of PON1 may be associated with these changes.
OBJECTIVE: To study the relationship between the lactonase activities and status of paraoxonase 1 (PON1) and its association with the PON1 genetic polymorphisms in women with polycystic ovarian syndrome (PCOS). DESIGN: A case-control study. METHODS: A total of 455 PCOSpatients and 441 control women were included in this study. The lactonase activities and concentrations of PON1 were assayed using 5-thiobutyl butyrolactone (TBBL) and 7-O-diethylphosphoryl-3-cyano-4-methyl-7-hydroxycoumarin (DEPCyMC) respectively. A normalized lactonase activity (NLA) was estimated based on the ratio of TBBLase:DEPCyMCase activity. The PON1 genotypes, serum malondialdehyde (MDA) levels and total antioxidant capacity were analyzed. RESULTS: The lactonase activities and levels of PON1 were higher in PCOSpatients than in the control women. However, the NLA did not significantly differ between groups. The -108C→T variation of the PON1 gene showed decreased lactonase activities and levels of PON1 in a genotype-dependent manner (CC>CT>TT); the 192Q→R variation of the PON1 gene showed increased PON1 lactonase activities and NLA; and the 55L→M variation of the PON1 gene showed decreased lactonase activities and levels of PON1 but an increased NLA. A multivariable regression analysis showed that the -108C/T, 192Q/R, and 55L/M variations of the PON1 gene, serum apolipoprotein A1, and MDA levels were significant predictors of PON1 lactonase activity, PON1 level, and NLA. CONCLUSIONS: The serum lactonase activities and concentrations of PON1 are increased in PCOSpatients. The increased oxidative stress and the -108C/T, 192Q/R, and 55L/M genetic polymorphisms of PON1 may be associated with these changes.