Association of insulin receptor genetic variants with polycystic ovary syndrome in a population of women from Central Europe Felicia A. Hanzu, M.D.,

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Association of insulin receptor genetic variants with polycystic ovary syndrome in a population of women from Central Europe Felicia A. Hanzu, M.D., Serban Radian, M.D., Ph.D., Redha Attaoua, Ph.D., Samira Ait-El-Mkadem, Ph.D., Simona Fica, M.D., Monica Gheorghiu, M.D., Mihai Coculescu, M.D., Ph.D., Florin Grigorescu, M.D., Ph.D. Fertility and Sterility Volume 94, Issue 6, Pages 2389-2392 (November 2010) DOI: 10.1016/j.fertnstert.2010.04.029 Copyright © 2010 American Society for Reproductive Medicine Terms and Conditions

Figure 1 Molecular analysis of INSR gene in patients with polycystic ovary syndrome (PCOS) from a Romanian population. (A) Linkage disequilibrium (LD) plot of single nucleotide polymorphisms (SNPs) near exon 9 of INSR gene. The gene structure is shown at the top (spanning >181 kb) and the cassette represents the gene fragment of 267 bp sequenced. The LD plot was displayed in Haploview and composed of four SNPs for which D' values are indicated in boxes. Red boxes indicate complete LD. In blue are indicated the ancestral alleles of SNPs drawn from the chimpanzee genome (Pan troglodytes). (B) Cladogram of INSR haplotypes. Haplotypes were inferred with PHASE program whereas the tree was constructed with ARLEQUIN software and drawn in WebPhylip. Sequences are presented from 5′ to 3′. Haplotypes are indicated in gray as described in Europeans with all SNPs from h1 to h9 as obtained as output in the PHASE program and disregarding their frequency. Underlined bases are those differing from the ancestral haplotype (AGTC-C). Hyphen indicates the link with the neighboring nucleotide of rs2962. (C) Correlation between the levels of total T and prevalence of the T allele of rs2963. Prevalence of genotypes is represented as distribution of haplotype pairs containing h9 haplotype (heterozygous h9 haplotypes are depicted in gray and homozygous 9/9 pairs in black). Testosterone levels in patients were analyzed as centiles with cutoff values of 2.3, 3.0, and 3.4 mmol/L. The SEM is indicated on the top of each group A (n = 45), B (n = 40), and C (n = 30). ∗Significant difference between groups by Student-Newman-Keuls test. Fertility and Sterility 2010 94, 2389-2392DOI: (10.1016/j.fertnstert.2010.04.029) Copyright © 2010 American Society for Reproductive Medicine Terms and Conditions