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Neuropeptide S receptor gene Asn107 polymorphism in obese male individuals in Pakistan.

ABSTRACT: Neuropeptide S (NPS) is a naturally occurring appetite stimulant, associated with anxiety, stress, and excitement regulation. Neuropeptide S serves as a hypothalamic energy regulator that enhances food intake with a reduced level of satiety. NPS activates fat angiogenesis and the proliferation of new adipocytes in obesity. NPS has an established role in energy regulation by many pre-clinical investigations; however we have limited data available to support this notion in humans. We found significant association of Neuropeptide S receptor (NPSR1) Asn107Ile (rs324981, A>T) polymorphism with obese male participants. The current investigation carried out genotype screening of NPSR1 allele to assess the spectrum of the Asn107Ile polymorphism in obese and healthy Pakistani individuals. We revealed a significant (p = 0.04) difference between AA vs TT + AT genotype distribution of NPSR1 (SNP rs324981,) between obese and healthy individuals (p = 0.04). In this genotype analysis of (SNP rs324981) of the NPSR1 gene, T allele was marked as risk allele with higher frequency in the obese (38%) compared to its frequency in the controls (25%). Single Nucleotide Polymorphism (SNP, rs324981) Asn107Ile of NPSR1gene, that switches an amino acid from Asn to Ile, has been found associated with increased susceptibility to obesity in Pakistani individuals. Furthermore, molecular simulation studies predicted a lower binding affinity of NPSR1 Asn107Ile variant to NPS than the wild-type consistent with the genotype studies. These molecular simulation studies predict a possible molecular mechanism of this interaction by defining the key amino acid residues. However, a significantly (p<0.0001) lower concentration of NPS was recorded independent of genotype frequencies in obese subjects compared to healthy controls. We believe that large scale polymorphism data of population for important gene players including NPSR1 will be more useful to understand obesity and its associated risk factors.

SUBMITTER: Ahmad A

PROVIDER: S-EPMC7745988 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Neuropeptide S receptor gene Asn107 polymorphism in obese male individuals in Pakistan.

Ahmad Aftab A Almsned Fahad F Ghazal Pasha P Ahmed Malik Waqar MW Jafri M Saleet MS Bokhari Habib H

PloS one 20201217 12

Neuropeptide S (NPS) is a naturally occurring appetite stimulant, associated with anxiety, stress, and excitement regulation. Neuropeptide S serves as a hypothalamic energy regulator that enhances food intake with a reduced level of satiety. NPS activates fat angiogenesis and the proliferation of new adipocytes in obesity. NPS has an established role in energy regulation by many pre-clinical investigations; however we have limited data available to support this notion in humans. We found signifi ...[more]

PMID: 33332443

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Project description:ObjectiveThe pathogenesis of schizophrenia is associated with neuropeptide Y (NPY) gene polymorphism to explore the relationship between rs16141, rs16145, and rs5573 polymorphisms in the NPY gene and antipsychotics response in the Chinese population.MethodsThe unrelated 228 Chinese Han patients with schizophrenia were enrolled in the present study. Genotypisation within NPY gene was performed using the KASP genotyping assays. Before treatment and on the weekends of the 2nd, 4th, and 8th weeks after treatment, the medication status of the patients was recorded and the positive and negative syndrome scale (PANSS) was used to evaluate the clinical effect. A reduction in total PANSS scores ≥50% were classified as good responders, while others were poor responders. We evaluated the association between NPY gene and antipsychotic efficacy by comparing allele and genotype distribution, correlation analysis, linkage imbalance, and five genetic models between the two groups.ResultsNo significant associations were found in the rs16141, rs16145, and rs5573 of NPY and antipsychotic treatment response (all p > 0.05). There was no significant relationship between the three SNPs polymorphisms in the NPY gene and the changes of positive, negative and general psychopathology subscales scores at each stage (all p > 0.05). The distribution of genotype and allele frequencies of locus rs16141 was not statistically difference between good responders and poor responders (genotype: χ2 =4.088, p=0.043, p-correction = 0.129; allele: χ2 = 4.088, p = 0.027, p-correction = 0.081). The allele distribution of rs5573 was significantly different between groups, yet the difference was disappeared after correcting (χ2 = 4.136, p = 0.042, p-correction =0.126). The distribution frequencies of TA/TG and GG haplotypes constituted by rs16141 and rs5573 showed no statistical difference between the two groups (p > 0.05). In recessive inheritance mode, NPYrs5573 was found to be associated with antipsychotic drug response (G/G vs. A/A +A/G: p = 0.028, AIC = 197.2, BIC = 210.9).ConclusionsThis study didn't found association between polymorphisms in the NPY gene locus (rs16141, rs16145, and rs5573) and the response to antipsychotics after Bonferroni correction. The polymorphism of NPY gene and the efficacy of antipsychotic drugs in patients with schizophrenia need further study.

Dataset Information

Neuropeptide S receptor gene Asn107 polymorphism in obese male individuals in Pakistan.

Publications

Neuropeptide S receptor gene Asn107 polymorphism in obese male individuals in Pakistan.

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