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

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

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

Background: Previous 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. Methods: A 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. Results: Alcohol 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. Conclusion: NPY rs16147:T>C might be correlated with susceptibility for depression in males during alcohol dependence withdrawal. The findings support the differential susceptibility model.

Neuropeptide Y Gene × Environment Interaction Predicts Resilience and Positive Future Focus.

BACKGROUND: The objective of this study was to investigate whether the NPY rs16147 polymorphism interacts with the environment to have an impact on resilience and positive future focus. METHODS: In Study 1, 1,140 earthquake survivors were evaluated; self-reported trauma exposure level and resilience were reported. Study 2 included 2,370 company employees and university students; information regarding self-reported early stressful life events and positive future focus were obtained. RESULTS: In both studies, the results showed a significant effect of interaction between the NPY rs16147 polymorphism and the level of stress on resilience. In Study 1, the T allele carriers reported consistent levels of resilience in low, moderate, and high levels of trauma exposure. In Study 2, the T genotype was associated with higher levels of positive future focus following early adversity. CONCLUSIONS: Our findings are discussed in light of the differential post-stress growth hypothesis.