Roshan Dadachanji1, Nuzhat Shaikh1, Sushma Khavale1, Anushree Patil2, Nalini Shah3, Srabani Mukherjee4. 1. Department of Molecular Endocrinology, National Institute for Research in Reproductive Health (ICMR), Mumbai, India. 2. Department of Clinical Research, National Institute for Research in Reproductive Health (ICMR), Mumbai, India. 3. Department of Endocrinology, Seth GS Medical College, Mumbai, India. 4. Department of Molecular Endocrinology, National Institute for Research in Reproductive Health (ICMR), Mumbai, India. Electronic address: mukherjees@nirrh.res.in.
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.
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 obesewomen.
Authors: Mohammad Ashraf Ganie; Vishnu Vasudevan; Imtiyaz Ahmad Wani; Mohammad Salem Baba; Tasleem Arif; Aafia Rashid Journal: Indian J Med Res Date: 2019-10 Impact factor: 2.375