Genetic variation in exon 17 of INSR is associated with insulin resistance and hyperandrogenemia among lean Indian women with polycystic ovary syndrome.
OBJECTIVE
Polycystic ovary syndrome (PCOS) is a multigenic disorder, and insulin resistance is one of its hallmark features. Polymorphisms in exon 17 of insulin receptor (INSR) gene are reported to be associated with PCOS. We investigated this association in Indian women and its putative relationship with PCOS associated traits, which has not been explored so far.


METHODS
In this case control study, the polymorphisms were investigated by direct sequencing in 180 women with PCOS and 144 age matched controls. Clinical, anthropometric, biochemical, and hormonal parameters were also estimated.


RESULTS
The silent C/T polymorphism at His1058 in exon 17 of INSR was found to be present in our study population. The polymorphic genotype (CT+TT) was significantly associated with PCOS in lean women (chi(2)=8.493, df=1, P=0.004). It showed association with higher fasting insulin levels (P=0.02), homeostasis model assessment of insulin resistance (P=0.005), free androgen index (P=0.03), and lower quantitative insulin sensitivity check index (P=0.004) in lean PCOS women. No other novel or known polymorphism was identified in exon 17 in this cohort.


CONCLUSIONS
The study shows significant association of C/T polymorphism at His1058 of INSR with PCOS in the lean rather than obese Indian women. Its association with indices of insulin resistance and hyperandrogenemia is also seen in the same group. The findings strengthen the concept that pathogenesis of PCOS is different in lean and obese women.
Mukherjee
Srabani
S
Department of Molecular Endocrinology, National Institute for Research in Reproductive Health, Indian Council of Medical Research (ICMR), Jehangir Merwanji Street, Parel, Mumbai 400012, India. mukherjees@nirrh.res.in
Shaikh
Nuzhat
N
Khavale
Sushma
S
Shinde
Gayatri
G
Meherji
Pervin
P
Shah
Nalini
N
Maitra
Anurupa
A
D000293:Adolescent; D000328:Adult; D015703:Antigens, CD / Q000235:genetics*; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D014644:Genetic Variation / Q000502:physiology*; D006801:Humans; D017588:Hyperandrogenism / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D007194:India; D007333:Insulin Resistance / Q000235:genetics*; D009765:Obesity / Q000150:complications / Q000235:genetics / Q000378:metabolism; D011085:Polycystic Ovary Syndrome / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D011972:Receptor, Insulin / Q000235:genetics*; D013851:Thinness / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
D015703:Antigens, CD; C435941:INSR protein, human; D011972:Receptor, Insulin