PON1 polymorphisms are associated with polycystic ovary syndrome susceptibility related traits and PON1 activity in Indian women with the syndrome

Authors:
Roshan Dadachanji, M.Sc., Nuzhat Shaikh, M.Sc., Sushma Khavale, B.Sc., Anushree Patil, M.D., Nalini Shah, M.D., Srabani Mukherjee, Ph.D.

Volume 104, Issue 1, Pages 207-216

Abstract:

Objective:
To investigate the association of paraoxonase 1 (PON1) polymorphisms (L55M and Q192R) with polycystic ovary syndrome (PCOS) susceptibility and its related traits in Indian women.

Design:
Case-control study.

Setting:
Academic research institute, infertility, and endocrinology clinics.

Patient(s):
Controls (n = 326), women with PCOS (n = 482).

Intervention(s):
None.

Main Outcome Measure(s):
Genotypic and allelic frequency distribution, genotype-phenotype association, different PON1 activities (lactonase, arylesterase, and paraoxonase).

Result(s):
The genotypic and allelic frequency distributions of the L55M polymorphism were significantly different between lean controls and lean women with PCOS, and this polymorphism reduced the risk of PCOS development in lean but not in obese Indian women. Furthermore, this polymorphism was significantly associated with decreased 2-hour glucose, apolipoprotein B, free and bioavailable T, and free androgen index concurrent with increased sex hormone-binding globulin (SHBG) and FSH levels only in lean women with PCOS. However, Q192R polymorphism showed comparable genotypic frequency distribution between controls and women with PCOS. PON1 lactonase and arylesterase activities were significantly decreased in women with PCOS compared with controls. PON1 polymorphisms were shown to influence its activities.

Conclusion(s):
Our study showed that L55M, but not Q192R, polymorphism is significantly associated with reduced PCOS susceptibility only in lean women and also impacts glucose metabolism, lipid parameters, and hyperandrogenemia in them. Our study therefore suggests the possibility of differential genetic pathophysiology of PCOS between lean and obese women.

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