Genetic contributions to pain modulation in sickle cell: A focus on single nucleotide polymorphisms

IF 1 Q4 GENETICS & HEREDITY Gene Reports Pub Date : 2024-07-18 DOI:10.1016/j.genrep.2024.101983

Katrina R. Hamilton , Lakeya S. McGill , Claudia M. Campbell , Sophie M. Lanzkron , C. Patrick Carroll , Alban Latremoliere , Jennifer A. Haythornthwaite , Olga A. Korczeniewska

{"title":"Genetic contributions to pain modulation in sickle cell: A focus on single nucleotide polymorphisms","authors":"Katrina R. Hamilton , Lakeya S. McGill , Claudia M. Campbell , Sophie M. Lanzkron , C. Patrick Carroll , Alban Latremoliere , Jennifer A. Haythornthwaite , Olga A. Korczeniewska","doi":"10.1016/j.genrep.2024.101983","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>Despite recent advances in our knowledge of genetic contributions to the highly variable sickle cell disease (SCD) phenotype, our understanding of genetic factors associated with pain sensitivity in SCD remains limited. Previous studies investigated specific variants in single candidate genes and their association with SCD pain variability. The primary aim of the current study was to expand the genes and polymorphisms tested to discover new risk genes (polymorphisms) associated with central sensitization for individuals with SCD.</p></div><div><h3>Methods</h3><p>Adults with sickle cell disease (<em>n</em> = 59, Mage = 36.8 ± 11.5, 65.8 % female) underwent quantitative sensory testing to examine central sensitization and general pain sensitivity. Participants reported average crisis and non-crisis pain intensities weekly using a 0–100 scale, and provided salivary samples for genotyping. The Hardy-Weinberg equilibrium was verified for controls, and allele distributions were tested with chi-square and odds ratio tests. The Benjamini-Hochberg procedure was used to control for false discovery rate. Regression analyses and Wilcoxon tests were used to test associations for normally distributed and skewed data, respectively.</p></div><div><h3>Results</h3><p>Central sensitization and general pain sensitivity were not associated with hemoglobin genotype (Ps > 0.05). Of 4145 SNPs tested, following false discovery rate adjustments, 11 SNPs (rs11575839, rs12185625, rs12289836, rs1493383, rs2233976, rs3131787, rs3739693, rs4292454, rs4364, rs4678, rs6773307) were significantly associated with central sensitization, and one SNP (rs7778077) was significantly associated with average weekly non-crisis pain. No SNPs were associated with general pain sensitivity.</p></div><div><h3>Conclusions</h3><p>These findings provide insights into genetic variants association with average non-crisis pain and central sensitization for individuals with SCD, and may provide support for genetic predictors of heightened pain experience within SCD.</p></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":null,"pages":null},"PeriodicalIF":1.0000,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452014424001067/pdfft?md5=d0ce5a99748c8e96dd1bc6e7d74d7d48&pid=1-s2.0-S2452014424001067-main.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Gene Reports","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2452014424001067","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}

引用次数: 0

Abstract

Background

Despite recent advances in our knowledge of genetic contributions to the highly variable sickle cell disease (SCD) phenotype, our understanding of genetic factors associated with pain sensitivity in SCD remains limited. Previous studies investigated specific variants in single candidate genes and their association with SCD pain variability. The primary aim of the current study was to expand the genes and polymorphisms tested to discover new risk genes (polymorphisms) associated with central sensitization for individuals with SCD.

Methods

Adults with sickle cell disease (n = 59, Mage = 36.8 ± 11.5, 65.8 % female) underwent quantitative sensory testing to examine central sensitization and general pain sensitivity. Participants reported average crisis and non-crisis pain intensities weekly using a 0–100 scale, and provided salivary samples for genotyping. The Hardy-Weinberg equilibrium was verified for controls, and allele distributions were tested with chi-square and odds ratio tests. The Benjamini-Hochberg procedure was used to control for false discovery rate. Regression analyses and Wilcoxon tests were used to test associations for normally distributed and skewed data, respectively.

Results

Central sensitization and general pain sensitivity were not associated with hemoglobin genotype (Ps > 0.05). Of 4145 SNPs tested, following false discovery rate adjustments, 11 SNPs (rs11575839, rs12185625, rs12289836, rs1493383, rs2233976, rs3131787, rs3739693, rs4292454, rs4364, rs4678, rs6773307) were significantly associated with central sensitization, and one SNP (rs7778077) was significantly associated with average weekly non-crisis pain. No SNPs were associated with general pain sensitivity.

Conclusions

These findings provide insights into genetic variants association with average non-crisis pain and central sensitization for individuals with SCD, and may provide support for genetic predictors of heightened pain experience within SCD.

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

镰状细胞疼痛调节的遗传贡献：聚焦单核苷酸多态性

背景尽管最近我们对遗传因素对多变的镰状细胞病（SCD）表型的影响有了进一步的了解，但我们对与 SCD 疼痛敏感性相关的遗传因素的了解仍然有限。以前的研究调查了单个候选基因的特定变异及其与 SCD 疼痛变异性的关系。本研究的主要目的是扩大测试的基因和多态性，以发现与 SCD 患者中枢敏感性相关的新风险基因（多态性）。方法对患有镰状细胞病的成人（n = 59，年龄 = 36.8 ± 11.5，65.8% 为女性）进行定量感觉测试，以检查中枢敏感性和一般疼痛敏感性。参与者每周用0-100分报告危机和非危机疼痛强度的平均值，并提供唾液样本进行基因分型。对照组的哈代-温伯格平衡得到了验证，等位基因分布则通过卡方检验和几率比验进行了检验。本杰明-霍奇伯格程序用于控制误发现率。回归分析和 Wilcoxon 检验分别用于检验正态分布数据和偏态分布数据之间的关联。在测试的 4145 个 SNPs 中，经过假发现率调整后，11 个 SNPs（rs11575839、rs12185625、rs12289836、rs1493383、rs2233976、rs3131787、rs3739693、rs4292454、rs4364、rs4678、rs6773307）与中枢敏感性显著相关，1 个 SNPs（rs7778077）与平均每周非危机疼痛显著相关。这些研究结果为了解遗传变异与 SCD 患者平均非危机性疼痛和中枢敏感化的关系提供了见解，并可能为 SCD 患者疼痛体验加剧的遗传预测因素提供支持。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊

Gene Reports Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

3.30

自引率

7.70%

发文量

246

审稿时长

49 days

期刊介绍： Gene Reports publishes papers that focus on the regulation, expression, function and evolution of genes in all biological contexts, including all prokaryotic and eukaryotic organisms, as well as viruses. Gene Reports strives to be a very diverse journal and topics in all fields will be considered for publication. Although not limited to the following, some general topics include: DNA Organization, Replication & Evolution -Focus on genomic DNA (chromosomal organization, comparative genomics, DNA replication, DNA repair, mobile DNA, mitochondrial DNA, chloroplast DNA). Expression & Function - Focus on functional RNAs (microRNAs, tRNAs, rRNAs, mRNA splicing, alternative polyadenylation) Regulation - Focus on processes that mediate gene-read out (epigenetics, chromatin, histone code, transcription, translation, protein degradation). Cell Signaling - Focus on mechanisms that control information flow into the nucleus to control gene expression (kinase and phosphatase pathways controlled by extra-cellular ligands, Wnt, Notch, TGFbeta/BMPs, FGFs, IGFs etc.) Profiling of gene expression and genetic variation - Focus on high throughput approaches (e.g., DeepSeq, ChIP-Seq, Affymetrix microarrays, proteomics) that define gene regulatory circuitry, molecular pathways and protein/protein networks. Genetics - Focus on development in model organisms (e.g., mouse, frog, fruit fly, worm), human genetic variation, population genetics, as well as agricultural and veterinary genetics. Molecular Pathology & Regenerative Medicine - Focus on the deregulation of molecular processes in human diseases and mechanisms supporting regeneration of tissues through pluripotent or multipotent stem cells.