Lactonase Activity, Status, and Genetic Variations of Paraoxonase 1 in Women with Gestational Diabetes Mellitus

Background. Paraoxonase 1 (PON1) is a calcium-dependent multifunctional enzyme that binds to high-density lipoproteins. The physiological function of PON1 is related to its lactonase activity. However, this activity has not been analyzed in women with gestational diabetes mellitus (GDM). The present...

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Main Authors: Mi Zhou, Xing-Hui Liu, Qing-Qing Liu, Meng Chen, Huai Bai, Lin-Bo Guan, Ping Fan
Format: Article
Language:English
Published: Wiley 2020-01-01
Series:Journal of Diabetes Research
Online Access:http://dx.doi.org/10.1155/2020/3483427
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author Mi Zhou
Xing-Hui Liu
Qing-Qing Liu
Meng Chen
Huai Bai
Lin-Bo Guan
Ping Fan
author_facet Mi Zhou
Xing-Hui Liu
Qing-Qing Liu
Meng Chen
Huai Bai
Lin-Bo Guan
Ping Fan
author_sort Mi Zhou
collection DOAJ
description Background. Paraoxonase 1 (PON1) is a calcium-dependent multifunctional enzyme that binds to high-density lipoproteins. The physiological function of PON1 is related to its lactonase activity. However, this activity has not been analyzed in women with gestational diabetes mellitus (GDM). The present study investigated the lactonase activities and status of PON1 and their association with PON1 genetic variants and oxidative stress indices in Chinese women with GDM. Methods. This is a case-control study of 347 women with GDM and 288 women with uncomplicated pregnancies. PON1 levels and lactonase activities were analyzed using 7-O-diethylphosphoryl-3-cyano-4-methyl-7-hydroxycoumarin (DEPCyMC) and 5-thiobutyl butyrolactone (TBBL), respectively. A normalized lactonase activity (NLA) was estimated based on the ratio of TBBLase to DEPCyMCase activity. Serum malondialdehyde (MDA), total oxidant status (TOS), total antioxidant capacity (TAC) levels, and PON1 genetic polymorphisms were also analyzed. Results. PON1 lactonase activity and levels of TOS, TAC, and MDA were higher in the GDM women compared with the control women. The PON1 -108C→T genetic variation decreased the levels and lactonase activities of PON1 in a genotype-dependent manner in the patient and control groups. GDM patients with the PON1 -108TT genotype displayed lower NLA than those with the -108CC or -108CT genotype. GDM patients with the RR genotype of PON1 192Q/R polymorphism had significantly lower PON1 lactonase activities and NLA and tended to have decreased PON1 levels compared with those with the QQ or QR genotype. Multivariable regression analysis revealed that the PON1 -108C/T or 192Q/R variations, apolipoprotein (apo) A1, apoB, TAC, MDA, or age was significant predictors of the levels, lactonase activities, or NLA of PON1. Conclusions. The lactonase activities of PON1 are increased in women with GDM. PON1 genetic variants, increased oxidative stress, and abnormalities in lipoproteins may be associated with these changes.
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spelling doaj-art-d0cada3a0c7c4ea291c0753eef9c8ff52025-08-20T02:20:03ZengWileyJournal of Diabetes Research2314-67452314-67532020-01-01202010.1155/2020/34834273483427Lactonase Activity, Status, and Genetic Variations of Paraoxonase 1 in Women with Gestational Diabetes MellitusMi Zhou0Xing-Hui Liu1Qing-Qing Liu2Meng Chen3Huai Bai4Lin-Bo Guan5Ping Fan6Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, 610041 Sichuan, ChinaDepartment of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, 610041 Sichuan, ChinaLaboratory 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, 610041 Sichuan, ChinaDepartment of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, 610041 Sichuan, ChinaLaboratory 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, 610041 Sichuan, ChinaLaboratory 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, 610041 Sichuan, ChinaLaboratory 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, 610041 Sichuan, ChinaBackground. Paraoxonase 1 (PON1) is a calcium-dependent multifunctional enzyme that binds to high-density lipoproteins. The physiological function of PON1 is related to its lactonase activity. However, this activity has not been analyzed in women with gestational diabetes mellitus (GDM). The present study investigated the lactonase activities and status of PON1 and their association with PON1 genetic variants and oxidative stress indices in Chinese women with GDM. Methods. This is a case-control study of 347 women with GDM and 288 women with uncomplicated pregnancies. PON1 levels and lactonase activities were analyzed using 7-O-diethylphosphoryl-3-cyano-4-methyl-7-hydroxycoumarin (DEPCyMC) and 5-thiobutyl butyrolactone (TBBL), respectively. A normalized lactonase activity (NLA) was estimated based on the ratio of TBBLase to DEPCyMCase activity. Serum malondialdehyde (MDA), total oxidant status (TOS), total antioxidant capacity (TAC) levels, and PON1 genetic polymorphisms were also analyzed. Results. PON1 lactonase activity and levels of TOS, TAC, and MDA were higher in the GDM women compared with the control women. The PON1 -108C→T genetic variation decreased the levels and lactonase activities of PON1 in a genotype-dependent manner in the patient and control groups. GDM patients with the PON1 -108TT genotype displayed lower NLA than those with the -108CC or -108CT genotype. GDM patients with the RR genotype of PON1 192Q/R polymorphism had significantly lower PON1 lactonase activities and NLA and tended to have decreased PON1 levels compared with those with the QQ or QR genotype. Multivariable regression analysis revealed that the PON1 -108C/T or 192Q/R variations, apolipoprotein (apo) A1, apoB, TAC, MDA, or age was significant predictors of the levels, lactonase activities, or NLA of PON1. Conclusions. The lactonase activities of PON1 are increased in women with GDM. PON1 genetic variants, increased oxidative stress, and abnormalities in lipoproteins may be associated with these changes.http://dx.doi.org/10.1155/2020/3483427
spellingShingle Mi Zhou
Xing-Hui Liu
Qing-Qing Liu
Meng Chen
Huai Bai
Lin-Bo Guan
Ping Fan
Lactonase Activity, Status, and Genetic Variations of Paraoxonase 1 in Women with Gestational Diabetes Mellitus
Journal of Diabetes Research
title Lactonase Activity, Status, and Genetic Variations of Paraoxonase 1 in Women with Gestational Diabetes Mellitus
title_full Lactonase Activity, Status, and Genetic Variations of Paraoxonase 1 in Women with Gestational Diabetes Mellitus
title_fullStr Lactonase Activity, Status, and Genetic Variations of Paraoxonase 1 in Women with Gestational Diabetes Mellitus
title_full_unstemmed Lactonase Activity, Status, and Genetic Variations of Paraoxonase 1 in Women with Gestational Diabetes Mellitus
title_short Lactonase Activity, Status, and Genetic Variations of Paraoxonase 1 in Women with Gestational Diabetes Mellitus
title_sort lactonase activity status and genetic variations of paraoxonase 1 in women with gestational diabetes mellitus
url http://dx.doi.org/10.1155/2020/3483427
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