Genetic variation in leptin and leptin receptor genes is a risk factor for idiopathic recurrent spontaneous abortion

Abstract

AimTo determine whether maternal leptin (LEP) and leptin receptor (LEPR) gene polymorphisms are associated with idiopathic recurrent spontaneous abortion (IRSA).MethodsThis case-control association study conducted from 2010 to 2012 at the Department of Gynecology and Obstetrics, University Hospital Center Osijek and Clinical Institute of Medical Genetics Ljubljana included 178 women with a history of three or more IRSAs before the 22nd week of gestation and 145 women with at least two live births and no history of pathologic pregnancies during reproductive period. Polymorphisms of maternal LEP (rs7799039, rs2122627, rs11761556, rs10244329) and LEPR (rs1137101, rs7516341, rs1186403, rs12062820) were assessed by allele specific real-time polymerase chain reaction. Genotype distribution, allele frequencies, and frequency of haplotypes at LEP and LEPR genetic loci were determined.ResultsWe observed more frequent genotype for rs7516341 (nominal P = 0.034, odds ratio [OR] 0.61, 95% confidence interval [CI] 0.38-0.97) and rs1137101 (nominal P = 0.048, OR 1.66, 95% CI 1.00-2.80) in the LEPR gene in patients than in controls, but these results did not remain significant after correction for multiple testing according to Bonferroni (adjusted P value threshold was set at 0.05). We did not observe differential distribution of genotype frequencies in the LEP gene between cases and controls. In patients with IRSA, GTCC haplotype in the LEPR gene locus was significantly less frequent than in controls (P = 0.00865, OR 0.45), contrary to ACTC haplotype (P = 0.0087, OR 1.98).ConclusionsWe showed that genetic variability in the LEPR gene was associated with IRSA, warranting confirmation on a greater number of patients and pathogenesis investigation.

Leptin action in normal and pathological pregnancies

“… did not find a correlation between this polymorphism and recurrent miscarriage. However, other studies have reported that these genetic variants are associated with pregnancy recurrent loss (Table ) .…”

The association of polymorphisms in promoter region of MMP2 and MMP9 with recurrent spontaneous abortion risk in Chinese population

“…[ 4 ] Certainly, genetic background is widely paid attention by scholars and a number of genes are discovered to be associated with RSA development, such as LEPR , MTHFR , and factor V genes. [ 5 , 6 ] Recently, with the development of molecular techniques, various genetic variants have been confirmed to be associated with RSA occurrence risk.…”

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

“…The association of LEPR gene with pathologies, including obesity [ 20 ], diabetes [ 17 , 22 ], pregnancy complications [ 28 – 30 ], cancer [ 31 , 32 ] was investigated in several populations. Few studies on Caucasian and Asian populations examined the association of LEPR genetic variants with PCOS, but with inconclusive findings, and an ethnic contribution to this association was suggested.…”

“…combination of LEPR pair of SNPs. This was followed by the construction of 3-locus haplotypes by the expectation maximization method, using the default method of Gabriel [28]. Multiple comparisons were corrected for by Bonferroni method, according to: corrected P (Pc) = 1− [1 − P) n ]; n denoting number of comparisons.…”