Investigating the hormone profile of adults with KISS1 p.Q36R variant and its effect on fertility in the Maltese population

Abstract

Idiopathic Hypogonadotropic hypogonadism (IHH) is a condition which is characterised by the lack or delayed sexual development of an individual. KISS1 codes for kisspeptin which is an endogenous ligand to KISS1R which plays an important role in reproduction, onset of puberty development, controlling the hypothalamic-pituitary-gonadal (HPG) axis and secretion of Luteinizing hormone and Follicle stimulating Hormone. Loss of kisspeptin signalling is seen to result in Hypogonadotropic hypogonadism (HH), where KISS1 is one of the many genes that are involved in HH. Some genetic variants of KISS1 have been reported to affect neuron migration to the hypothalamus, an important process in the formation of the HPG axis which is essential in signalling of the pituitary gland to release hormones. One variant which has been identified in this gene is p.Q36R. This variant was found to have a variable frequency in different populations but in a recent study this variant was found in higher frequency in individuals with IHH thus, the variant has been suggested to increase risk of IHH. As this is not a rare variant, this raises the question if the KISS1 p.Q36R variant does indeed affect hormone levels and fertility in an individual, and whether it has this affect in the heterozygous or homozygous state. In this study, hormone data and genotype data from 1098 individuals from the MAMI study was used to investigate the effect of the KISS1 p.Q36R variant (rs35431622) on hormone levels including testosterone, oestradiol, Follicle stimulating hormone (FSH), Luteinizing hormone (LH), Dehydroepiandrosterone (DHEA) Sulfate and sex hormone binding globulin (SHBG). Median hormone levels were investigated in men and women separately divided into suitable age groups and no differences were found between the median levels of individuals with or without the p.Q36R variant. Based on the findings of this study the KISS1 p.Q36R variant is unlikely to play a role in infertility of the Maltese population.