■尽管我们对高度可变的镰状细胞病(SCD)表型的遗传贡献的认识有了最新进展,我们对与SCD疼痛敏感性相关的遗传因素的理解仍然有限.先前的研究调查了单个候选基因的特定变异及其与SCD疼痛变异性的关联。当前研究的主要目的是扩展测试的基因和多态性,以发现与SCD个体的中枢致敏相关的新风险基因(多态性)。
■患有镰状细胞病的成年人(n=59,Mage=36.8±11.5,女性65.8%)接受了定量感觉测试,以检查中枢致敏和一般疼痛敏感性。参与者每周使用0-100量表报告平均危机和非危机疼痛强度,并提供唾液样本进行基因分型。哈代-温伯格平衡得到了对照的验证,和等位基因分布用卡方检验和比值比检验。Benjamini-Hochberg程序用于控制错误发现率。回归分析和Wilcoxon检验用于测试正态分布和偏斜数据的关联,分别。
■中枢致敏和全身疼痛敏感性与血红蛋白基因型无关(Ps>0.05)。在测试的4145个SNP中,在错误发现率调整后,11个SNP(rs11575839,rs12185625,rs12289836,rs1493383,rs223976,rs3131787,rs3739693,rs4292454,rs4364,rs4678,rs6773307)与中枢致敏显著相关,一个SNP(rs7778077)与平均每周非危象性疼痛显著相关。没有SNP与一般疼痛敏感性相关。
■这些发现为SCD患者提供了遗传变异与平均非危象性疼痛和中枢致敏的关系的见解。并且可能为SCD中疼痛经历加剧的遗传预测因子提供支持。
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.