Circulating leptin concentration, LEP gene variants and haplotypes, and polycystic ovary syndrome in Bahraini and Tunisian Arab women

Abstract

Background and aim: Epidemiological studies suggested that ethnic/racial background influences the associations of altered leptin secretion and leptin gene (LEP) polymorphisms with polycystic ovary syndrome (PCOS). We investigated the association between LEP variants and plasma leptin levels with PCOS in Tunisian and Bahraini Arab women.

Subjects and methods: Retrospective case-control study, involving 255 PCOS cases and 253 control subjects from Bahrain, and 320 women PCOS cases and 447 controls from Tunisia. LEP genotyping was done by allele exclusion on real-time PCR.

Results: Minor allele frequencies of rs10487506, rs7799039, rs2167270, rs12706832, and rs10954173 LEP variants were not significantly different between PCOS cases and control women among Bahraini and Tunisians, even before applying the Bonferroni correction. Similarly, the genotype distribution of the tested LEP variants was comparable between women with PCOS and control women among Bahraini and Tunisian subjects. None of the tested LEP variants was linked with altered leptin serum concentrations. However, five-locus haplotype analysis identified GGGGG and GAGGG haplotypes to be positively, and haplotype AAGGG to be negatively associated with PCOS in Bahraini women, after adjusting for HOMA-IR. No LEP haplotype associated with PCOS was identified in Tunisians.

Conclusion: This is the first study to document differential contribution of LEP gene variants with PCOS according to ethnic/racial background of study subjects, highlighting the need for controlling for ethnicity in genetic association studies.

Keywords: Genotyping; Haplotypes; Leptin; Polycystic ovary syndrome; Polymorphisms.