Leutinizing hormone/choriogonadotropin receptor and follicle stimulating hormone receptor gene variants and risk of recurrent pregnancy loss: a case control study

Abstract

We investigated the association of luteinizing hormone/chorionic gonadotropin receptor (LHCGR) and follicle stimulating hormone receptor (FSHR) polymorphisms with recurrent pregnancy loss (RPL). This was a retrospective case-control study involving 308 women with RPL and 310 control women. FSHR and LHCGR genotyping was done by allelic exclusion method. Lower minor allele frequency (MAF) of LHCGR rs7371084, and rs4597581, and FSHR rs6166, and higher MAF of rs1007541, and rs2055571 FSHR variants were seen in RPL cases. Significantly lower frequencies of heterozygous LHCGR rs2293275, rs7371084, and rs4597581, and homozygous FSHR rs6166, and higher frequency of homozygous FSHR rs2055571 carriers were seen in RPL cases, after controlling for key covariates. LHCGR rs7371084 and rs4597581 were negatively associated with RPL in non-obese subjects. On the other hand, FSHR rs1007541 and rs2055571 were positively, while FSHR rs6166 was negatively associated with RPL in obese subjects. Limited linkage disequilibrium was seen only among FSHR variants; higher frequency of GTAAA and AAGGA, and lower frequency of GTGGG FSHR haplotypes was seen in RPL cases; the frequencies of remaining FSHR haplotypes, and all LHCGR haplotypes were similar between cases and controls. This is the first study to demonstrate association of novel LHCGR (rs7371084 and rs4597581) and FSHR (rs6166, rs1007541 and rs2055571) SNPs with RPL, particularly according to obesity.