KISS1 Gene Polymorphisms Research Articles

An association between fat mass and obesity-associated (FTO) (rs9939609) and kisspeptin-1 (KISS-1) (rs4889, rs372790354) gene polymorphisms with polycystic ovary syndrome: an updated meta-analysis and power analysis.

The present meta-analysis aimed to investigate FTO rs9939609 and KISS1 rs4889, rs372790354 gene polymorphisms and its association with PCOS in Asian population. The studies included in this article were obtained by using online databases. We searched databases such as Scopus, PubMed, Embase, and Web of Science for case-control articles related to FTO and KISS1 gene polymorphism with PCOS. Metagenyo software was used to determine the 95% confidence interval (CI) and odds ratio (OR). A total of 13 articles was included in this meta-analysis for FTO (rs9939609) and KISS1 (rs4889; rs372790354) gene polymorphisms related with PCOS in the Asian population. According to the findings of this study, people with FTO rs9939609 show an association with PCOS risk in dominant model. On contradictory, KISS1 gene polymorphism specifically, rs4889 show an association with PCOS risk in allelic, recessive, and dominant models whereas rs372790354 show an association with PCOS risk in allelic and dominant models. Power analysis was performed and PPI is > 0.04. The sting analysis network for FTO and KISS1 gene estimated 12 nodes and 23 edges. The FTO rs9939609 variant exhibits an association with an increased risk of PCOS in the dominant model. KISS1 gene polymorphism, particularly rs4889, shows a significant association with PCOS risk in allelic, recessive, and dominant models. Similarly, KISS1 rs372790354 gene is associated with PCOS risk in both allelic and dominant models. Researches were focused only on the Asian population so; it is imperative to conduct further research across diverse populations.

Polymorphism rs5780218, rs12998 and rs10158616 in KISS1 gene among the Hubei province Chinese girls with the central precocious puberty.

Central precocious puberty (CPP) results from early activation of the hypothalamic-pituitary-gonadal (HPG) axis. To elucidate the molecular genetic basis of CPP, we here investigated the effects of polymorphism rs5780218, rs12998 and rs10158616 in KISS1 gene on CPP susceptibility. The three KISS1 gene polymorphisms were genotyped by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and Sanger sequencing in 422 healthy Hubei Chinese girls and 384 Hubei Chinese girls with CPP. Single-locus analysis demonstrated that rs5780218 and rs12998 were significantly associated with CPP susceptibility in Hubei Chinese girls. Haplotype analysis exhibited that the AGG carrying the risk allele A of rs5780218 and the -GG carrying the protective allele - of rs5780218 were associated with increased and decreased CPP susceptibility in Hubei Chinese girls, respectively. The following meta-analysis confirmed the contribution of rs5780218 and rs12998 on CPP susceptibility in Chinese girls. rs5780218 and rs12998 in the KISS1 gene may participate in genetic susceptibility to CPP in Chinese girls, and the KISS1 gene rs5780218 may serve as a genetic biomarker of CPP. However, the present findings should be validated in future studies with larger sample sizes in other ethnic populations.

Novel g.2055A>C and g.2064T>A Polymorphisms of KISS1 Gene and Its Association with Reproductive Traits in Local Indonesian Goats

Kisspeptins are known as neuropeptides encoded by the KISS1 gene, which potentiates GnRH neuron excitability. Unfortunately, the role of the KISS1 gene in reproductive traits remains unclear in Indonesian native goat breeds. The current study purposed to detect the genetic variation of the KISS1 gene and investigate the association with reproductive traits in goats to acquire marker-assisted selection (MAS) for the breeding program. Further, ninety blood samples from randomly selected animals were used for DNA isolation and SNP genotyping. The blood serum was collected from sixteen treated goat does to assess FSH levels using ELISA method. The differences between studied parameters were determined using independent samples T-test from SAS Software. Two SNPs, g.2055A>C (SNP1) and g.2064T>A (SNP2) were discovered in intron 1 of KISS1 gene in Indonesian native goat breeds. Two genotypes were identified from each SNPs: AA and AC at SNP1 and TT and TA at SNP2. The allele A (0.96) at SNP1 and allele T (0.93) at SNP2 were discovered as dominant alleles in the population. Furthermore, chi-square test showed that both SNPs were under Hardy-Weinberg equilibrium. The variants of KISS1 gene have no effect on litter size (p>0.05). Moreover, AA genotype of SNP1 had a higher FSH level than that observed in AC genotype (p<0.0001), especially in the follicular phase. SNP2 does not correlate with FSH level relatively (p=0.23). Furthermore, using of AA genotype at SNP1 of KISS1 gene as MAS for the breeding selection program could escalate the reproductive traits in goats

Relevance of KISS1 gene polymorphisms in susceptibility to polycystic ovary syndrome and its associated endocrine and metabolic disturbances

ABSTRACT Background: Variations in KISS1 may be an emerging factor in polycystic ovary syndrome (PCOS) We hypothesised links between KISS1 polymorphisms in PCOS and its associated endocrine and metabolic disturbances. Methods: The study included 104 PCOS women and 109 controls. Endocrine (kisspeptin, LH, FSH, LH-FSH ratio, oestradiol) and metabolic (cholesterol, triglycerides, HDL, LDL, insulin and glucose) parameters were measured. PCR and nucleotide sequencing were carried out to screen single nucleotide polymorphisms (SNPs) of KISS1. Endocrine and metabolic parameters of PCOS women were compared in the genotypes. Results: Three novel SNPs (rs1213704663C>G, rs1481572212T>G and rs775770652G>A) were detected in KISS1. Of these SNPs, the genotype and allele frequencies of rs1213704663C>G were all significantly associated p<0.001 with PCOS. The LH and oestradiol hypersecretion, and increased LH-FSH ratio of PCOS women were significantly influenced by the GG genotype of rs1213704663, but, this SNP did not influence kisspeptin levels. The other two SNPs rs1481572212T>G and rs775770652G>A exhibited no clinical significance. Conclusion: rs1213704663C>G variation in KISS1 is linked to PCOS and its associated endocrine and metabolic disturbances (LH and oestradiol hypersecretion, and increased LH/FSH).

Influence of KISS1 gene polymorphisms on the risk of polycystic ovary syndrome and its associated variables, in Saudi women

BackgroundPolycystic ovary syndrome (PCOS) is a complex multifactorial disorder, affecting millions of women worldwide. The role of genetic polymorphisms of the KISS1 gene on the development of PCOS is still obscure. This study was designed to investigate the probable influence of KISS1 gene polymorphisms on PCOS and its associated variables: BMI, waist-hip ratio, kisspeptin, LH, FSH, and LH-FSH ratio.MethodsThe study comprised 104 PCOS women and 109 controls, with age ranging from 19 to 36 years. BMI, waist-hip ratio, and circulating levels of kisspeptin, LH, and FSH were measured. DNA was extracted, and genotyping of the KISS1 gene was carried out by nucleotide sequencing. The PCOS-associated variables were analyzed in different genotypes of single nucleotide polymorphisms (SNPs) of the KISS1 gene.ResultsThe values of waist-hip ratio (WHR), LH, and LH-FSH ratio were significantly higher in PCOS women than controls. BMI, kisspeptin, and FSH levels exhibited no significant difference between the groups. Six novel SNPs of KISS1 gene were identified. Three: rs372790354G > A, rs12998G > A, and rs35431622A > T were investigated. Among these SNPs, the genotype and allele frequencies of rs372790354 showed significant association with PCOS (GA: p = 0.018, AA: p = 0.022, mutant allele-A: p = 0.021) and the G allele was protective. The values of LH, kisspeptin, and WHR of PCOS women were significantly influenced (p < 0.05) by the AA genotype of rs372790354. The other two SNPs rs12998G > A and rs35431622A > T revealed no significant influence on PCOS and associated variables. Haplotypes were constructed, but there was no significant difference between the patients and controls.ConclusionIn conclusion, this is the first study, which reports a significant influence of KISS1 gene polymorphism (rs372790354G > A) on PCOS and its associated variables. However, more extensive research is necessary to confirm these findings.

Rs4889 polymorphism in KISS1 gene, its effect on polycystic ovary syndrome development and anthropometric and hormonal parameters in Saudi women

BackgroundKisspeptin is involved in female reproduction. This study was designed to i- estimate kisspeptin levels in women with polycystic ovary syndrome (PCOS), in comparison with controls, ii- study the correlations between kisspeptin and PCOS-related reproductive hormones, and iii- investigate the relation between KISS1 gene polymorphisms and hormone levels in women suffering from PCOS.MethodsThe investigation was a clinically designed study on 28 women with PCOS, and 30 normal, healthy women with no signs of PCOS as controls. Blood samples were collected between day 3 and day 6 of the menstrual cycle in both groups at 8:00 a.m., and circulating levels of LH, FSH and kisspeptin were estimated. DNA was extracted from whole blood and all coding exons of KISS1 gene were sequenced.ResultsWomen with PCOS had higher LH levels and BMI compared to controls. Plasma kisspeptin levels were positively correlated with LH levels. There was no statistically significant difference between the groups in terms of kisspeptin and FSH levels. The SNP rs4889 C/G, a non-synonymous SNP, was investigated in the PCOS group. The frequency of GG genotype was significantly higher in the PCOS compared to the controls. These patients were more obese, had higher kisspeptin and FSH levels.ConclusionThe results of the study show that the genetic variation of KISS1 gene may be a factor contributing to PCOS development. The association between the gene and the gene variation and PCOS need further validation in large-scaled and functional studies.

English

Genetic information especially of the Quantitative Trait Loci (QTL) which affect different performance traits is considered one of the most effective tools in the breeding programs of livestock. Several genes were reported as candidate genes that effect litter size performance and one of these genes is the KISS1 which is considered as a regulator of puberty onset. The polymorphisms of KISS1 gene have some relationships with high prolific and sexual precocity. The objective of this study was the detection of the restriction fragment length polymorphism (RFLP) and single nucleotide polymorphisms (SNPs) of KISS1 gene in six major Egyptian small ruminant breeds. The primers used in this study flanked a 377 bp fragment from intron 1 of KISS1 gene in sheep and goat. These PCR amplified fragments were digested with XmnI endonuclease. According to the presence or absence of the restriction site (GAANN^NNTTC) at position 121^122, we genotyped the 122 tested animals as AT (54.92%) and TT (45.08) with the absence of AA genotype. The overall frequencies of alleles A and T were 27.46 and 72.54%, respectively. The sequence analysis of purified PCR products representing these two detected genotypes declared the presence of a SNP (T→A) at position 125 in the amplified fragment which is responsible for the elimination of the restriction site and consequently the presence of two different alleles T and A. The nucleotide sequences of sheep KISS1 alleles T and A as well as goat KISS1 alleles T and A were submitted to GenBank database and have accession numbers: KP835797, KP835798, KP835799 and KP835800, respectively. It is concluded that small ruminant breeds have high frequency of KISS1 allele T which was associated with greater litter size. We recommend to increase this allele in Egyptian small ruminant breeds and also to select the animals which possess TT genotypes of KISS1 gene and enter them in breeding programs of Egyptian small ruminants to increase their fecundity traits. Key words: Sheep, goat, KISS1, polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP), single nucleotide polymorphisms (SNPs).

Association analysis between variants in KISS1 gene and litter size in goats

BackgroundKisspeptins are the peptide products of KISS1 gene, which operate via the G - protein-coupled receptor GPR54. These peptides have emerged as essential upstream regulators of neurons secreting gonadotropin-releasing hormone (GnRH), the major hypothalamic node for the stimulatory control of the hypothalamic–pituitary– gonadal (HPG) axis. The present study detected the polymorphisms of caprine KISS1 gene in three goat breeds and investigated the associations between these genetic markers and litter size.ResultsThree goat breeds (n = 680) were used to detect single nucleotide polymorphisms (SNPs) in the coding regions with their intron–exon boundaries and the proximal flanking regions of KISS1 gene by DNA sequencing and PCR–RFLP. Eleven novel SNPs (g.384G>A, g.1147T>C, g.1417G>A, g.1428_1429delG, g.2124C>T, g.2270C>T, g.2489T>C, g.2510G>A, g.2540C>T, g.3864_3865delCA and g.3885_3886insACCCC) were identified. It was shown that Xinong Saanen and Guanzhong goat breeds were in Hardy-Weinberg disequilibrium at g.384G>A locus (P < 0.05). Both g.2510G>A and g.2540C>T loci were closely linked in Xinong Saanen (SN), Guanzhong (GZ) and Boer (BG) goat breeds (r2 > 0.33). The g.384G>A, g.2489T>C, g.2510G>A and g.2540C>T SNPs were associated with litter size (P<0.05). Individuals with AATTAATT combinative genotype of SN breed (SC) and TTAATT combinative genotype of BG breed (BC) had higher litter size than those with other combinative genotypes in average parity. The results extend the spectrum of genetic variation of the caprine KISS1 gene, which might contribute to goat genetic resources and breeding.ConclusionsThis study explored the genetic polymorphism of KISS1 gene, and indicated that four SNPs may play an important role in litter size. Their genetic mechanism of reproduction in goat breeds should be further investigated. The female goats with SC1 (AATTAATT) and BC7 (TTAATT) had higher litter size than those with other combinative genotypes in average parity and could be used for the development of new breeds of prolific goats. Further research on a large number of animals is required to confirm the link with increased prolificacy in goats.

Serum Kisspeptin Levels in Korean Girls with Central Precocious Puberty

Central precocious puberty (CPP) is caused by premature activation of hypothalamic gonadotropin-releasing hormone (GnRH) secretion. Kisspeptin and G-protein coupled receptor-54 system is the essential gatekeeper of the reproductive system, playing a key role in the activation of the gonadotropic axis at puberty. We aimed to determine whether serum kisspeptin may function as a marker for CPP by investigating serum kisspeptin levels in Korean girls with CPP and their prepubertal controls. Serum kisspeptin levels of Korean girls with CPP (n = 30) and age-matched healthy prepubertal controls (n = 30) were measured with a competitive enzyme immunoassay. Serum kisspeptin levels were significantly higher in CPP group than in control group (4.61 ± 1.78 vs 2.15 ± 1.52 pM/L, P < 0.001). Serum kisspeptin was positively correlated with peak luteinizing hormone (LH), peak/basal LH ratio and peak LH/follicular-stimulating hormone (FSH) ratio during GnRH stimulation test. CPP is supposed to be triggered by premature increase of kisspeptin. Serum kisspeptin may be used as a marker of CPP. Further studies on KISS1 gene polymorphisms leading to higher risk of premature increase of kisspeptin and upstream regulator of kisspeptin are also needed.

New genetic polymorphisms of KiSS-1 gene and their association with litter size in goats

In the present study, the polymorphisms of kisspeptin (KiSS-1) gene were analyzed in 652 individuals from three goat breeds: Xinong Saanen goats (SG), Guanzhong goats (GZ) and Boer goats (BG). Three alleles (T, C and G) and four genotypes (TT, TC, CC and TG) were detected in the intron 2 of KiSS-1 gene by PCR-SSCP analysis. In addition, two single nucleotide polymorphisms (SNPs) – T2643C and 8bp base deletions (2677AGTTCCCC) were identified by DNA sequencing. The SNPs loci were in Hardy–Weinberg disequilibrium in three goat breeds (P<0.05). After comparing genotypic distribution within three goat breeds, BG had conspicuous differences from SG and GZ (P<0.001). Association of polymorphism with litter size was done in SG and GZ breeds, which showed to be associated with litter size in both goat breeds. The SNP in goat KiSS-1 gene had significant effects on litter size (P<0.05). Therefore, these results suggest that KiSS-1 gene is a strong candidate gene that affects litter size in goats.