Characterisation of KiSS1R gene and Non genetic factors affecting reproductive traits in Indian goats

This study was undertaken to explore the genetic polymorphism in the KiSS1R (GPR54) gene from 80 Black Bengal, 50 Ganjam and 20 Raighar goat. Each of the sampled goats was recorded for its reproductive traits. The genomic DNA was isolated from the collected blood samples. The target 3’ UTR comprising of 246 bp fragment of KiSS1R gene was successfully amplified using the specific primer. Amplified samples were subjected for HRM analysis followed by sequencing. The nucleotide sequence alignment with the retrieved DNA sequence from NCBI BLAST confirmed absence of polymorphic pattern in KiSS1R gene in 3’ UTR. However, in the studied populations breed had significant effect on littersize, kidding interval and age at sexual maturity. It was found that age at sexual maturity and kidding interval were the highest in Ganjam goat population as compared to Raighar and Black Bengal goat population. Litter size was found highest in Black Bengal goat.

Association of Kiss1 and GPR54 Gene Polymorphisms with Polycystic Ovary Syndrome among Sri Lankan Women

Polycystic ovary syndrome (PCOS) is the commonest endocrine disorder affecting women of reproductive age. Its aetiology, though yet unclear, is presumed to have an oligogenic basis interacting with environmental factors. Kisspeptins are peptide products of Kiss1 gene that control the hypothalamic pituitary (HPG) axis by acting via G protein-coupled receptor known as GPR54. There is paucity of data on the role of Kiss1 and GPR54 gene in PCOS. We aimed to identify the polymorphisms in Kiss1 and GPR54 genes and explore their association with serum kisspeptin levels among Sri Lankan women with well-characterized PCOS. Consecutive women with PCOS manifesting from adolescence (n=55) and adult controls (n=110) were recruited. Serum kisspeptin and testosterone levels were determined by ELISA method. Whole gene sequencing was performed to identify the polymorphisms in Kiss1 and GPR54 genes. Serum kisspeptin and testosterone concentrations were significantly higher in women with PCOS than controls: kisspeptin 4.873nmol/L versus 4.127nmol/L; testosterone 4.713nmol/L versus 3.415 nmol/L, p<0.05. Sequencing the GPR54 gene revealed 5 single nucleotide polymorphisms (SNPs), rs10407968, rs1250729403, rs350131, chr19:918686, and chr19:918735, with two novel SNPs (chr19:918686 and chr19:918735), while sequencing the Kiss1 gene revealed 2 SNPs, rs5780218 and rs4889. All identified SNPs showed no significant difference in frequency between patients and controls. GPR54 gene rs350131 polymorphism (G/T) was detected more frequently in our study population. The heterozygous allele (AG) of GPR54 gene novel polymorphism chr19:918686 showed a marginal association with serum kisspeptin levels (p=0.053). Genetic variations in GPR54 and Kiss1 genes are unlikely to be associated with PCOS among Sri Lankan women manifesting from adolescence. Meanwhile the heterozygous allele of chr19:918686 is probably associated with serum kisspeptin concentrations, which suggests a potential role in the aetiology of PCOS.

Role of Kisspeptin in Female Infertility

Background: Kiss1, a noble G protein coupled receptor designated as GPR54, was first identified in rat brain in 1999 and orthologue gene identified in human in 2001 the original niche for the function of kisspeptin was restricted to cancer biology for their ability to suppress tumor metastasis. However, kisspeptin has recently emerged as a key player in the field of reproductive endocrinology.Method: A systematic literature review was done by using PUBMED. Though there is lack of human data, used animal data also hold translational potential for human. Results: Inactivating mutation of GPR54 gene is linked with absence of puberty onset and idiopathic hypogonadotrophic hypogonadism. Furthermore, recent studies support critical role of kisspeptin/GPR54 system on regulation of GnRH neurons, involvement of puberty onset and gonadal steroid feedback.Conclusion: This review will briefly discuss on cellular and molecular level of kisspeptin, their potential effects on human and clinical application of kisspeptin on human reproductive disorder.Pulse Vol.8 January-December 2015 p.43-50