Neuropeptide Y Rs16147 Research Articles

Pain-related single nucleotide polymorphisms: association with lumbar spinal stenosis patient experience and non-surgical treatment outcomes.

Lumbar spinal stenosis (LSS) is common in our aging population resulting in pain and functional impairment. Recent advances in pain research have identified several single nucleotide polymorphisms (SNP) associated with inter-individual symptom and treatment response. The goal of the current study was to investigate the association of SNPs in Neuropeptide Y (NPY) and Catechol-O-methyltransferase (COMT) with pain, function, and treatment outcomes in Lumbar spinal stenosis (LSS) patients receiving non-surgical treatments. An exploratory observational biomarker study was performed ancillary to a previously published clinical trial evaluating three different non-surgical treatments for LSS. Saliva samples were obtained for single nucleotide polymorphism genotyping and blood samples were collected for NPY protein. Data on pain and function collected as part of the clinical trial at baseline, 2 and 6 months were examined for association with known polymorphisms in NPY and COMT. Subjects with the NPY rs16147 TT genotype exhibited higher baseline symptom severity but also a higher likelihood of responding to non-surgical treatments. Subjects with the COMT rs4680 GG genotype also exhibited higher baseline symptom severity but did not demonstrate greater response to treatment. NPY rs16147 and COMT rs4680 are important potential biomarkers associated with pain and function. NPY genotype may be useful in predicting response to non-surgical treatments in older adults with LSS.

Promoter polymorphisms of neuropeptide Y, interleukin-1B and increased IL-1β levels are associated with rheumatoid arthritis susceptibility in South Gujarat population

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint destruction. Interleukin-1B(IL-1β) has been implicated in RA, and neuropeptide Y (NPY) induces the release of pro-inflammatory cytokines including IL1-β, TNF-α and IL-6. Single nucleotide polymorphisms (SNPs) in NPY and IL1B gene may lead to their altered levels leading to RA pathogenesis. Therefore, we aimed to investigate association of NPY rs16147(T > C) SNP, and genotype–phenotype correlation of the IL1B rs16944(C > T) SNP in 302 RA patients and 337 controls by Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Both the genotype and allele frequencies for NPY rs16147(T > C)(p = 0.0019 &p = 0.012) and IL1B rs16944(C > T)(p = 0.0024 &p = 0.0014) SNPs differed significantly between RA patients and controls. The odds ratios of 1.23 and 1.47 for NPY rs16147(T > C) and IL1B rs16944(C > T) SNPs respectively, suggest that these SNPs may be genetic risk factor for RA in South Gujarat population. The plasma IL-1β levels(p = 0.0332) and genotype-phenotype correlation of IL1B rs16944(C > T) SNP suggested increased IL-1β levels, particularly in patients with susceptible ‘TT' genotypes(p < 0.0001). Additionally, plasma IL-1β level was significantly increased in severe RA patients (p = 0.0025) and positively correlated with Rheumatoid factor(RF) (r = 0.9240, p < 0.0001), suggesting the role of IL-1β in disease severity. Overall, the study for the first time suggests that NPY rs16147(T > C) and IL1B rs16944(C > T) SNPs may be associated with RA susceptibility in South Gujarat population. Additionally, the IL1B rs16944 susceptible ‘TT' genotype may lead to increased IL-1β levels, thereby contributing to RA pathogenesis and severity.

Neuropeptide Y gene variants and Agreeableness: interaction effect with the birth cohort and the serotonin transporter promoter polymorphism.

Neuropeptide Y (NPY) is a powerful regulator of anxious states, including social anxiety, but evidence from human genetic studies is limited. Associations of common gene variants with behaviour have been described as subject to birth cohort effects, especially if the behaviour is socially motivated. This study aimed to examine the association of NPY rs16147 and rs5574 with personality traits in highly representative samples of two birth cohorts of young adults, the samples having been formed during a period of rapid societal transition. Both birth cohorts (original n = 1238) of the Estonian Children Personality Behaviour and Health Study (ECPBHS) self-reported personality traits of the five-factor model at 25 years of age. A significant interaction effect of the NPY rs16147 and rs5574 and birth cohort on Agreeableness was found. The T/T genotype of NPY rs16147 resulted in low Agreeableness in the older cohort (born 1983) and in high Agreeableness in the younger cohort (born 1989). The C/C genotype of NPY rs5574 was associated with higher Agreeableness in the younger but not in the older cohort. In the NPY rs16147 T/T homozygotes, the deviations from average in Agreeableness within the birth cohort were dependent on the serotonin transporter promoter polymorphism. The association between the NPY gene variants and a personality domain reflecting social desirability is subject to change qualitatively in times of rapid societal changes, serving as an example of the relationship between the plasticity genes and environment. The underlying mechanism may involve the development of the serotonergic system.

The neuropeptide Y single-nucleotide polymorphism rs16147:T>C moderates the effect of alcohol dependence on depression in male Chinese Han population.

BackgroundPrevious studies suggest that alcohol dependence is associated with depression, however, the effect of alcohol dependence varies from individual to individual, which may be due to different genetic backgrounds. The interactions between alcohol dependence and different gene polymorphisms may finally shape the onset of depression. Neuropeptide Y (NPY), which can maintain homeostasis from high-stress stimulation, may protect individuals from the onset of depression. Here, we explored whether the NPY rs16147:T>C has an association with depression in individuals with alcohol dependence during the period of alcohol dependence withdrawal.MethodsA total of 455 males with alcohol dependence were recruited. The scale of Michigan Alcoholism Screening Test (MAST) and Self-Depression Scale (SDS) were respectively used to analyze the condition of alcohol dependence and depression. Genomic DNA was extracted from each blood sample and NPY polymorphisms were genotyped. The interaction between NPY rs16147:T>C and alcohol dependence on depression was first analyzed. Then, region of significance analysis was used to confirm which model provided the best fit for the interaction (diathesis-stress or differential susceptibility). Finally, by using internal replication analyses, the accuracy and robustness of the interaction results were improved.ResultsAlcohol dependence was positively correlated with depression. CC homozygotes of NPY rs16147:T>C exhibited less depression when exposed to low alcohol dependence, but more depression when exposed to high alcohol dependence. Individuals with the T allele showed the opposite result.ConclusionNPY rs16147:T>C might be correlated with susceptibility for depression in males during alcohol dependence withdrawal. The findings support the differential susceptibility model.

15 ROLE OF NEUROPEPTIDE Y GEN RS 16147 POLIMORFISM AS A RISK FACTOR FOR HYPERTENSION

Background: According to World Health Organization (WHO), hypertension has been a medical problem that associated with 7.5 millions (12.8 percents) death in wide world. Neuropeptide Y (NPY) is the most often found neurotransmitter in nervous system, comes from expression of NPY gen rs16147, has effect in symphatetic tonus enhancement result in increasing blood pressure (BP). Objective: To determine role of NPY Gen RS 16147 Polimorfism as a risk factor of hypertension. Method: Analytic study with case control design to determine relationship between NPY Gen RS 16147 Polimorfism: C-399T and BP with Chi Square test. Population consist of 100 sample (50 male,50 female) with consecutive sampling. Sample taken from venous blood, analyzed using Polymerase Chain Reaction Restriction Fragment Length Polymorphism (PCR-RFLP) method. p value &lt;0,05 means statistically significant. Result: Study enrolled subject with median age 51,5 (22—83) years (26 normotension, 74 hypertension), subject with alel “C” NPY RS 16147 genotype has abnormal BP, while subject with non alel “C” NPY RS 16147 (TT genotype) has both normal and abnormal BP, (p: 0.017). Average systolic blood pressure (SBP) in non alel “C” NPY RS 16147 genotype is 139,05±21,42 mmHg, while average SBP in alel “C” genotipe NPY RS 16147 genotype is 151,32±22,26 mmHg. Conclusion: Neuropeptide Y Gen RS 16147 polimorfism is a risk factor for hypertension. The presence of alel “C” in NPY RS16147 related to high BP significantly.

The Effect of Neuropeptide Y (NPY) rs 16147 Gene Polymorphism on the Blood Pressure of Chronic Kidney Disease Patients and Control Healthy in Medan, Indonesia

Introduction: Chronic Kidney Disease (CKD) is a pathological condition that occurs gradually and is irreversible, characterized by structural and functional abnormalities in the kidneys that lasts for more than three months. The C allele in the Neuropeptide Y (NPY) RS16147 gene is closely related to an increase in the incidence of hypertension, a decrease in glomerular filtration rate, and an increase in total cholesterol levels in CKD patients. Objective: To determine the effect of the NPY RS16147 gene polymorphism on the blood pressure of chronic kidney disease patients and control healthy in Medan Indonesia. Methods: This study is an analytical study with a case-control design at the Haji Adam Malik General Hospital Medan from July to August 2020. All subjects had Deoxyribonucleic Acid (DNA) analysis using Polymerase Chain Reaction Restriction Fragment Length Polymorphism (PCR-RFLP) method. Results: We obtained 100 study subjects, 43 was CKD patients with dialysis, 31 CKD patients without dialysis, and 26 control healthy groups. In this study, there were differences in the trend genotypes of NPY RS16147 polymorphism with the incidence of CKD and control healthy. We obtained a significant difference the mean systolic blood pressure patients with genotypes TT (139,05±21,42) and TC/CC (151,32±22,26) as evidenced by the value of P = 0.00 (≤0.05). The presence of the "C" allele in the NPY RS16147 gene sample increased blood pressure in all study subjects significantly (P=0.028; ≤0.05). Conclusion: the "C" allele in the NPY RS16147 gene affects systolic blood pressure. Keywords: NPY RS16147 polymorphism, Chronic kidney disease, Blood pressure.

Relationship Between Alcohol Dependence and Neuropeptide Y (NPY) Gene Promoter Polymorphisms in A Turkish Sample

Neuropeptide Y (NPY) is a protein widely expressed in the central nervous system and involved in diverse physiological processes, such as emotional regulation, nutritional behavior, and stress. In some populations, studies on alcohol dependence (AD) and the NPY gene have found that NPY variations increase alcohol consumption and thus may potentially be associated with AD. In this study, we investigated the relationship between NPY gene promoter polymorphisms and phenotypes related to alcohol use. A total of 417 male participants comprising 252 individuals with AD and 165 healthy individuals were included in this study and phenotypic data were collected. Polymerase chain reaction-restriction fragment length polymorphism (PCR/RFLP) and DNA sequencing METHODS were used for genotyping the rs16147 and rs17149106 polymorphisms in the promoter region of the NPY gene. The data of 384 participants were analysed to evaluate the possible relationship between genotypes and the diagnosis of AD, family history of AD, the severity of AD using the Michigan Alcoholism Screening Test (MAST), the age of onset of problematic alcohol use, the average amount of alcohol consumed per day for the last six months and the lifetime maximum alcohol consumption in one day. A significant difference was found between the AD and control groups concerning rs16147 polymorphism genotype distribution (p=0.025). No association with polymorphisms and alcohol-related phenotypes were demonstrated in the AD group. To our knowledge, this study shows for the first time in the literature that alcohol dependence is associated with NPY rs16147 polymorphism in the Turkish population.

Associations of Gene Variations in Neuropeptide Y and Brain Derived Neurotrophic Factor Genes with Posttraumatic Stress Disorder.

Individuals who are exposed to traumatic events are at an increased risk of developing posttraumatic stress disorder (PTSD), a condition during which an individual's ability to function is impaired by emotional responses to memories of those events. The gene coding for neuropeptide Y (NPY) and the gene coding for brain-derived neurotrophic factor (BDNF) are among the number of candidate gene variants that have been identified as potential contributors to PTSD. The aim of this study was to investigate the association between NPY and BDNF and PTSD in individuals who experienced war-related trauma in the South Eastern Europe (SEE) conflicts (1991-1999). This study included participants with current and remitted PTSD and healthy volunteers (N=719, 232 females, 487 males), who were recruited between 2013 and 2015 within the framework of the South Eastern Europe (SEE) - PTSD Study. Psychometric methods comprised the Mini International Neuropsychiatric Interview (M.I.N.I.), the Clinician Administered PTSD Scale (CAPS), and the Brief Symptom Inventory (BSI). DNA was isolated from whole blood and genotyped for NPY rs5574 via PCR - RFLP and NPY rs16147 and BDNF rs6265 using the KASP assay. Tests for deviation from Hardy-Weinberg equilibrium showed no significant results. Analyses at the categorical level yielded no associations between the affected individuals and all three SNPs when compared to controls. Within lifetime PTSD patients, the major alleles of both NPY variants showed a nominally significant association with higher CAPS scores (p=0.007 and p=0.02, respectively). Also, the major allele of rs5574C>T was associated with higher BSI scores with a nominal significance among current PTSD patients (p=0.047). The results did not withstand a Bonferroni adjustment (α=0.002). Nominally significant associations between NPY polymorphisms and PTSD susceptibility were found that did not withstand Bonferroni correction.

ASSOCIATION OF NEUROPEPTIDE-Y -399 (T/C) GENE POLYMORPHISM AND ITS LEVEL WITH THE RISK OF TYPE-2 DIABETES MELLITUS

Neuropeptide-Y (NPY) is widely distributed centrally and peripherally and plays an important role in regulating glucose metabolism, energy metabolism and vascular function. Several studies had found that NPY is involved in the pathophysiology of type-2 diabetes Mellitus (T2DM). The aim of this study was to evaluate the association of NPY -399 (T/C) gene polymorphism and its serum level with susceptibility to T2DM. Seventy diabetic patients and seventy age and gender matched healthy controls were enrolled in this study. Serum NPY was measured by ELISA and NPY rs16147(-399 T/C) polymorphism was analyzed using the TaqMan allelic discrimination assay technique. Results showed significant statistical differences between the two studied groups regarding serum NPY level and NPY rs16147 (-399T/C) genotype distribution with increased serum NPY level and increased frequency of the CC and TC genotype in patients with diabetes mellitus. Conclusion: CC genotypes of NPY (-399 T/C) gene polymorphism and its associated high serum NPY level might be a genetic risk factor for T2DM.Keywords: Type-2 diabetes mellitus, neuropeptide-Y, insulin resistance, gene polymorphism.

Functional Polymorphism in the Neuropeptide Y Gene Promoter (rs16147) Is Associated with Serum Leptin Levels and Waist-Hip Ratio in Women

Objective: The neuropeptide-Y (NP-Y) gene is a strong candidate gene in the pathophysiology of obesity-linked behavior, and several single-nucleotide polymorphisms of NP-Y have already been linked to body weight and appetite. However, the results from current studies remain inconclusive. The aim of the present study was to test whether a certain functional genetic variant (SNP rs16147) in the NP-Y promoter gene is associated with serum leptin levels and body fat distribution. Method: We genotyped and measured the serum leptin levels of the NP-Y rs16147 polymorphism in 1,097 Caucasian subjects in the context of a population-based, case-control multicenter study. We measured weight, height and waist circumference, from which we then calculated BMI and waist-to-hip ratio (WHR). Results: We found the CT-genotype of the SNP rs16147 to be significantly associated with lower WHRs and higher serum leptin levels in women, compared to homozygote gene carriers. No association between rs16147, WHR and serum leptin levels was found in men. Conclusion: Our results provide evidence that the functionally relevant SNP in the NP-Y promoter gene affects body fat distribution and serum leptin levels in women, pointing towards possible behavioral effects of NPY in obesity.

Increasing association between a neuropeptide Y promoter polymorphism and body mass index during the course of development

To investigate the association of the neuropeptide Y (NPY) promoter polymorphism rs16147 with body mass index (BMI) during the course of development from infancy to adulthood. Longitudinal, prospective study of a German community sample. n = 306 young adults (139 males, 167 females). Participants' body weight and height were assessed at the ages of 3 months and 2, 4.5, 8, 11, 15 and 19 years. NPY rs16147 was genotyped. Controlling for a number of possible confounders, homozygote carriers of the rs16147 C allele exhibited significantly lower BMI scores when compared with individuals carrying the T allele. In addition, a significant genotype by age interaction emerged, indicating that the genotype effect increased during the course of development. This is the first longitudinal study to report an association between rs16147 and BMI during childhood and adolescence. The finding that this effect increased during the course of development may either be due to age-dependent alterations in gene expression or to maturation processes within the weight regulation circuits of the central nervous system.

An interaction between a neuropeptide Y gene polymorphism and early adversity modulates endocrine stress responses

Interindividual variability in the regulation of the human stress system accounts for a part of the individual's liability to stress-related diseases. These differences are influenced by environmental and genetic factors. Early childhood adversity is a well-studied environmental factor affecting an individual's stress response which has been shown to be modulated by gene-environment interaction (GxE). Neuropeptide Y (NPY) plays a role in stress regulation and genetic variation in NPY may influence stress responses. In this study, we analyzed the association of a common variant in the NPY gene promoter, rs16147, with cortisol and ACTH responses to acute psychosocial stress in young adults from the Mannheim Study of Children at Risk (MARS), an ongoing epidemiological cohort study following the outcome of early adversity from birth into adulthood. We found evidence of a GxE interaction between rs16147 and early adversity significantly affecting HPA axis responses to acute psychosocial stress. These findings suggest that the neurobiological mechanisms linking early adverse experience and later neuroendocrine stress regulation are modulated by a gene variant whose functional relevance is documented by increasing convergent evidence from in vitro, animal and human studies.

Neuropeptide Y (NPY) gene: Impact on emotional processing and treatment response in anxious depression

Neuropeptide Y (NPY) has been found to play a role in the pathomechanism of both anxiety and depression. Thus, NPY is a promising candidate in the investigation of the clinical phenotype of "anxious depression". Five NPY gene variants were investigated for an influence on antidepressant treatment response in a sample of 256 patients with depression. Additionally, NPY gene impact on amygdala activation during facial emotion processing was analyzed in a subsample of 35 depressed patients. Particularly in anxious depression, the less active NPY rs16147 -399C allele conferred slow response after 2weeks and failure to achieve remission after four weeks of treatment. The rs16147 C allele was further associated with stronger bilateral amygdala activation in response to threatening faces in an allele-dose fashion. The present results point towards a possible influence of functional NPY gene variation on antidepressant treatment response in anxious depression, potentially conveyed by altered emotional processing.