Meng W, Deshmukh H A, van Zuydam N R, Liu Y, Donnelly L A, Zhou K, Morris A D, Colhoun H M, Palmer C N A, Smith B H
Division of Population Health Sciences, Medical Research Institute, Ninewells Hospital and School of Medicine, University of Dundee, UK.
Eur J Pain. 2015 Mar;19(3):392-9. doi: 10.1002/ejp.560.
Neuropathic pain, caused by a lesion or a disease affecting the somatosensory system, is one of the most common complications in diabetic patients. The purpose of this study is to identify genetic factors contributing to this type of pain in a general diabetic population.
We accessed the Genetics of Diabetes Audit and Research Tayside (GoDARTS) datasets that contain prescription information and monofilament test results for 9439 diabetic patients, among which 6927 diabetic individuals were genotyped by Affymetrix SNP6.0 or Illumina OmniExpress chips. Cases of neuropathic pain were defined as diabetic patients with a prescription history of at least one of five drugs specifically indicated for the treatment of neuropathic pain and in whom monofilament test result was positive for sensory neuropathy in at least one foot. Controls were individuals who did not have a record of receiving any opioid analgesics. Imputation of non-genotyped SNPs was performed by IMPUTE2, with reference files from 1000 Genomes Phase I datasets.
After data cleaning and relevant exclusions, imputed genotypes of 572 diabetic neuropathic pain cases and 2491 diabetic controls were used in the Fisher's exact test. We identified a cluster in the Chr8p21.3, next to GFRA2 with a lowest p-value of 1.77 × 10(-7) at rs17428041. The narrow-sense heritability of this phenotype was 11.00%.
This genome-wide association study on diabetic neuropathic pain suggests new evidence for the involvement of variants near GFRA2 with the disorder, which needs to be verified in an independent cohort and at the molecular level.
由影响躯体感觉系统的损伤或疾病引起的神经性疼痛是糖尿病患者最常见的并发症之一。本研究的目的是在普通糖尿病患者群体中确定导致此类疼痛的遗传因素。
我们获取了泰赛德糖尿病遗传审计与研究（GoDARTS）数据集，其中包含9439名糖尿病患者的处方信息和单丝试验结果，其中6927名糖尿病个体通过Affymetrix SNP6.0或Illumina OmniExpress芯片进行了基因分型。神经性疼痛病例定义为有至少一种专门用于治疗神经性疼痛的五种药物之一的处方史且单丝试验结果显示至少一只脚存在感觉神经病变阳性的糖尿病患者。对照组为没有接受任何阿片类镇痛药记录的个体。通过IMPUTE2对未基因分型的单核苷酸多态性（SNP）进行推算，参考文件来自千人基因组计划一期数据集。
经过数据清理和相关排除后，在Fisher精确检验中使用了572例糖尿病神经性疼痛病例和2491例糖尿病对照的推算基因型。我们在8号染色体p21.3区域发现了一个聚类，紧邻GFRA2，在rs17428041处的最低p值为1.77×10⁻⁷。该表型的狭义遗传率为11.00%。
这项关于糖尿病神经性疼痛的全基因组关联研究为GFRA2附近的变异与该疾病的关联提供了新证据，这需要在独立队列和分子水平上进行验证。
