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HTR1B基因变异与手臂振动暴露工人雷诺现象的易感性相关。

HTR1B gene variants associate with the susceptibility of Raynauds' phenomenon in workers exposed hand-arm vibration.

作者信息

Chen Qingsong, Lang Li, Xiao Bin, Lin Hansheng, Yang Aichu, Li Hongling, Tang Shichuan, Huang Hanlin

机构信息

Guangdong Prevention and Cure Centre of Occupational Diseases, Guangzhou, China.

Key Laboratory of Occupational Health and Safety, Beijing Municipal Institute of Labor Protection, Beijing, China.

出版信息

Clin Hemorheol Microcirc. 2016 Oct 5;63(4):335-347. doi: 10.3233/CH-152021.

Abstract

OBJECTIVE

To explore whether polymorphic variants of the HTR1B gene are associated with the susceptibility of Raynauds' Phenomenon (RP) coursed by vibration.

METHODS

148 subjects exposed to vibration for more than 2 years were classified into either induced white finger (VWF) group (n = 72), or non-VWF group (n = 76). Vibration exposure levels were measured and assessed following ISO 5349-1:2001 protocol. All workers were genotyped by sequencing for the single nucleotide polymorphisms (SNPs) in the 5'-flanking and coding region of HTR1B. Genetic characteristics and linkage disequilibrium (LD) were analyzed with Haploview. Serum serotonin levels of each subject were detected using ELISA. The association between the susceptibility of vascular damage and genotype was analyzed via logistic regression.

RESULTS

7 known SNPs were obtained and their allele frequencies were inserted into the Hardy-Weinberg equilibrium. rs6297 variant genotype had an increased risk of VWF compared with wild genotype (OR = 2.14, 95% CI = 1.04- 4.58, P < 0.05). rs6298 mutant type (AG+GG) was found to have a significant interaction on vibration exposure LN(CEI), accounting for VWF occurrence. LN(5-HT) level is significantly different between the VWF group (x¯±s= 1.99±1.09 ng/mL) and the non-VWF group (x¯±s= 2.72±1.47 ng/mL).

CONCLUSIONS

Serotonin levels may affect the progression of secondary RP. Polymorphic variants of the HTR1B gene are associated with the susceptibility of secondary RP in vibration-exposed occupational populations of Chinese Han people.

摘要

目的

探讨5-羟色胺受体1B(HTR1B)基因多态性变异是否与振动诱发的雷诺现象(RP)易感性相关。

方法

将148名接触振动2年以上的受试者分为诱发白指(VWF)组(n = 72)和非VWF组(n = 76)。按照ISO 5349-1:2001标准测量和评估振动暴露水平。对所有工人进行HTR1B基因5′侧翼和编码区单核苷酸多态性(SNP)的测序基因分型。使用Haploview分析遗传特征和连锁不平衡(LD)。采用酶联免疫吸附测定(ELISA)法检测每位受试者的血清5-羟色胺水平。通过逻辑回归分析血管损伤易感性与基因型之间的关联。

结果

获得7个已知SNP,并将其等位基因频率纳入哈迪-温伯格平衡。与野生基因型相比,rs6297变异基因型发生VWF的风险增加(比值比[OR]=2.14,95%可信区间[CI]=1.04 - 4.58,P<0.05)。发现rs6298突变型(AG + GG)对振动暴露对数(转换能量指数)有显著交互作用,可解释VWF的发生。VWF组(x¯±s=1.99±1.09 ng/mL)与非VWF组(x¯±s=2.72±1.47 ng/mL)的5-羟色胺对数(LN[5-HT])水平有显著差异。

结论

5-羟色胺水平可能影响继发性RP进展。HTR1B基因多态性变异与中国汉族振动暴露职业人群继发性RP易感性相关。

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