Mo Ming-Shu, Xiao You-Sheng, Wu Zhuo-Hua, Sun Cong-Cong, Zhang Li-Min, Cen Luan, Chen Xiang, Qu Shao-Gang, Yang Xin-Ling, Xu Ping-Yi
Department of Neurology, First Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510000, China; Department of Neurology, First Affiliated Hospital of Guangzhou Medical UniversityGuangdong 510120, China.
Department of Neurology, First Affiliated Hospital of Sun Yat-sen University Guangzhou 510000, China.
Int J Physiol Pathophysiol Pharmacol. 2015 Dec 25;7(4):185-94. eCollection 2015.
Our aim is to explore the linkage between single nucleotide polymorphisms (SNPs) in human leukocyte antigen (HLA)-DRA and Parkinson's disease (PD). 542 sporadic PD patients and 674 healthy controls were recruited to investigate this association in the Chinese population by the screening of 15 SNPs in HLA-DRA, and the association of rs3129882 was further re-evaluated by performing meta-analysis and meta-regression analysis. No SNPs in HLA-DRA were significantly associated with PD in the Chinese patients. Although the rs3129882 allele-G frequency in the Caucasian population was lower than that in Chinese population, meta-analysis showed no association of rs3129882 allele-G with PD in the Chinese or Caucasian population. In consideration of the heterogeneity (I(2)=78.6%, Q=66.33, p<0.000), subgroup analysis was performed, revealing a significant association between rs3129882 and PD in the Caucasian patients from the genome-wide association studies (OR=1.22, 95% CI: 1.16, 1.27); however, this association was not consistently observed in the studies performed using other DNA sequencing techniques. Meta-regression analysis, which accounted for 58.3% of the heterogeneity, revealed that the impact of the sequencing technique used was significant (p=0.027) compared with ethnicity. Regression analysis of the Caucasian population further showed that the sequencing technique used contributed to 71.2% of the heterogeneity (p=0.033). Our data support the absence of a linkage between the risk loci in HLA-DRA and PD in Chinese patients. The different DNA sequencing techniques used in PD studies may largely account for the controversial conclusions concerning rs3129882.
我们的目标是探究人类白细胞抗原（HLA）-DRA中的单核苷酸多态性（SNP）与帕金森病（PD）之间的联系。招募了542例散发性PD患者和674名健康对照，通过筛查HLA-DRA中的15个SNP来研究中国人群中的这种关联，并通过进行荟萃分析和荟萃回归分析进一步重新评估rs3129882的关联。在中国患者中，HLA-DRA中的SNP与PD均无显著关联。尽管白种人群中rs3129882等位基因-G的频率低于中国人群，但荟萃分析表明，rs3129882等位基因-G与中国或白种人群的PD均无关联。考虑到异质性（I(2)=78.6%，Q=66.33，p<0.000），进行了亚组分析，结果显示在全基因组关联研究中，rs3129882与白种人患者的PD之间存在显著关联（OR=1.22，95%CI：1.16，1.27）；然而，在使用其他DNA测序技术进行的研究中并未一致观察到这种关联。荟萃回归分析解释了58.3%的异质性，结果显示与种族相比，所用测序技术的影响显著（p=0.027）。对白种人群的回归分析进一步表明，所用测序技术导致了71.2%的异质性（p=0.033）。我们的数据支持中国患者中HLA-DRA风险位点与PD之间不存在联系。PD研究中使用的不同DNA测序技术可能在很大程度上解释了关于rs3129882的有争议的结论。
