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

Abstract

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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“…However, because of limited funding and specimens, we did not measure the levels of other ROS/RNS markers. Furthermore, TAC represents the ability to eliminate free radicals 30 , and OSI (the ratio of TOS/TAC) can evaluate the balance of oxidation and anti-oxidation 31 . We found a slightly higher TAC in patients with PCOS than in those without PCOS, but the difference was not significant.…”

“…Using Trolox [(±) 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid] as a standard, the TAC (mmol Trolox Equiv./L) was determined based on the decolourisation of 2,2′-azinobis (3-ethylbenzothiazoline-6-sulphonate) (ABTS). Changes in the colour were measured as absorbance at 420 nm 30 . Using hydrogen peroxide (H 2 O 2 ) as a standard, the TOS (µmol H 2 O 2 Eq/L) was measured as the oxidation of ferrous to ferric ions by oxidant species in acidic medium.…”

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“…Superoxide dismutase (SOD) was determined using SOD kits (NanJing Jiancheng Bioengineering Institute Co. Ltd.) and spectrophotometry at 450 nm. The total antioxidant capacity (TAC) (mmol Trolox Equiv./L) and TOS (μmol H 2 O 2 Equiv./L) were measured by the semiautomatic microplate colorimetric method using hydrogen peroxide (H 2 O 2 ) and Trolox, respectively, for the standard [22,23]. The oxidative stress index (OSI) was expressed as the ratio of TOS to the TAC.…”

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