Contrasting association of Leptin receptor polymorphisms and haplotypes with polycystic ovary syndrome in Bahraini and Tunisian women: a case–control study

Background. This study examined the contribution of ethnicity to the
association of leptin receptor gene (LEPR) genetic variants with
polycystic ovary syndrome (PCOS) in Tunisian and Bahraini Arabic-speaking
women. Methods. Subjects consisted of 320 women with PCOS, and 446
eumenorrhic women from Tunisia, and 242 women with PCOS and 238 controls
from Bahrain. Genotyping of (exonic) rs1137100 and rs1137101 and
(intronic) rs2025804 LEPR variants was done by allelic exclusion. Results.
The minor allele frequencies of rs1137100 and rs1137101 were significantly
different between PCOS cases and control women from Bahrain but not
Tunisia, and LEPR rs1137101 was associated with increased PCOS
susceptibility only in Bahraini subjects. Furthermore, rs1137100 was
associated with decreased PCOS risk among Bahrainis under codominant and
recessive models; rs1137100 was negatively associated with PCOS in
Tunisians after controlling for testosterone. In addition, rs2025804 was
associated with increased PCOS risk among Tunisian but not Bahraini women,
after adjusting for key covariates. Negative correlation was seen between
rs1137101 and triglycerides in Tunisians, while HOMA-IR and insulin
correlated with rs2025804 and rs1137101 among Bahraini subjects, and
rs1137101 correlated with estradiol and prolactin. Taking TAG haplotype as
common, positive association of TAA and negative association of TGG
haplotype with PCOS was seen among Bahraini women; no three-locus
PCOS-associated haplotypes were found in Tunisians. Conclusions. This
study is the first to demonstrate the contribution of ethnicity to the
association of LEPR gene variants with PCOS, thereby highlighting the
significance of controlling for ethnicity in gene association
investigations.