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

Abstract

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.

Association of leptin G2548A and leptin receptor Q223R polymorphisms and their serum levels with infertility and recurrent pregnancy loss in Iranian women with polycystic ovary syndrome

“…This discrepancy may be due to the difference in the studied population. Although the association of rs7799039 and rs1137101 polymorphisms with some metabolic disorders including obesity, insulin resistance and dyslipidemia has been evaluated [ 25 – 28 ], few studies have been carried out on the association between these polymorphisms and PCOS [ 29 , 30 ]. The present study indicates for the first time the association of rs7799039 and rs1137101 polymorphisms with PCOS-related infertility in Iranian women.…”

“…The results of this study showed that rs1137101 polymorphism of the LEPR gene is associated with PCOS and PCOS-related infertility. There are conflicting data about the association between this polymorphism and PCOS in the different populations [ 29 , 59 ]. Li et.al showed that the G allele of rs1137101polymorphism is significantly associated with the decreased risk of PCOS in the Korean population [ 60 ].…”

“…Li et.al showed that the G allele of rs1137101polymorphism is significantly associated with the decreased risk of PCOS in the Korean population [ 60 ]. Recently, a study by Dallel et.al reported significantly different allele frequencies of rs1137101 polymorphism between PCOS subjects and control women from Bahrain [ 29 ]. They also indicated that the G allele of rs1137101 polymorphism is associated with the risk of PCOS in Bahraini women, while this association was not found in Tunisians [ 29 ].…”

“…Recently, a study by Dallel et.al reported significantly different allele frequencies of rs1137101 polymorphism between PCOS subjects and control women from Bahrain [ 29 ]. They also indicated that the G allele of rs1137101 polymorphism is associated with the risk of PCOS in Bahraini women, while this association was not found in Tunisians [ 29 ]. Moreover, Daghestani et.al showed no significant association between rs1137101 polymorphism of LEPR gene and PCOS in Saudi women [ 59 ].…”

“…Several studies have investigated the relationships between LEP G2548A/ LEPR Q223R polymorphisms and obesity, diabetes, insulin resistance, dyslipidaemias and cancer [ 25 – 28 ]. However, few studies have addressed the association between these two polymorphisms and PCOS [ 29 , 30 ]. Given the correlation between leptin, obesity, insulin action and reproductive functions, we hypothesized that plasma leptin and sOB-R levels, and also LEP / LEPR variants might be associated with PCOS as well as infertility and recurrent pregnancy loss (RPL) in PCOS patients.…”