Genes previously associated with Polycystic Ovary Syndrome (PCOS) in the Asian population and
variability in PCOS population from central Europe
R. Attaoua1, S. Haydar1, D. Fakih1, L. Andreasen1, M. Vintila2, A. Bensalem1, N. Baculescu2, C.
Normand1, P. Poucheret3, M. Coculescu2, F. Grigorescu1;
Molecular Endocrinology Laboratory, UMR204 NUTRIPASS, Université de Montpellier 1 (IURC),
France, 2Department of Endocrinology, University of Medicine and Pharmacy “Carol Davila”, Bucharest,
Romania, 3Pharmacology and Experimental Physiology Laboratory. Faculty of Pharmacy, Montpellier,
Background and aims: Recent investigations by genome-wide association approach in an Asian
population identified many genes associated with polycystic ovary syndrome (PCOS), as LHCGR
(luteinizing hormone/choriogonadotropin receptor), DENND1A (DENN/MADD domain containing 1A),
YAP1 (Yes-associated protein 1), TOX3 (TOX high mobility group box family member 3) and insulin
receptor (INSR) genes. In this context we explored variation of these genes and that of KLF14 (Kruppellike factor 14) gene in PCOS in a population of 401 cases and 143 controls from Central Europe well
characterized at the endocrine and metabolic levels, aiming to test gene association to PCOS in a
population of Caucasian origin.
Materials and methods: Genetic markers used in the study were the SNPs rs2479106 A/G, rs1894116
A/G, rs4784165 T/G, rs2059807 (A/G) and rs1562398 for DENND1A, YAP1, TOX3 and INSR,
respectively. Genotyping of SNPs was carried-out by KASPar technology while genetic association and
genotype-phenotype correlations were calculated by logistic regression and ANOVA, respectively using
StatView and GoldenHelix programs, respectively.
Results: We observed gene-dose effect of LHCGR (rs1340572) with diastolic blood pressure (P = 0.014;
GG (n =1) 100 mmHg, AG: (n = 33) 73,8 ± 3.2 mmHg, AA: (n = 224) 69.7 ± 0.8 mmHg) while
DENND1 (rs2479106) displayed a trend of gene-dose effect with plasma insulin at 120 minutes during
the OGTT test (P = 0.053; AA (n = 84): 73.8 ± 7.2 mU/L, AG (n = 101): 102.0 ± 10.9 mU/L, GG (n = 22)
128.3 ± 39.2 mU/L). However none of genes were associated with PCOS phenotype in our investigation.
Conclusion: This study allowed observing the association of genes with metabolic components of PCOS
with some variability from data previously reported in the Asian population, which highlights one more
time the necessity of considering differences between populations when studying the genetic
susceptibility to complex disorders.
Supported by: EC MEDIGENE FP7 project