Association analysis of STK39, MCCC1/LAMP3 and sporadic PD in the Chinese Han population
Association analysis of STK39, MCCC1/LAMP3 and sporadic PD in the Chinese Han population
复制标题
STK39、MCCC1/LAMP3与中国汉族人群散发性PD的关联分析
DOI：
10.1016/j.neulet.2014.03.007
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发表时间：
2014-04-30
影响因子：
2.5
通讯作者：
Guo, Ji-feng
中科院分区：
文献类型：
--
作者：
Wang, Ya-qin;Tang, Bei-sha;Guo, Ji-feng
随着人类基因组计划的完成，GWAS已被广泛应用于复杂疾病的遗传学研究。对来自美国和欧洲的5个帕金森病GWAS数据集的荟萃分析发现，11个位点超过了全基因组显著性阈值（p < 5 x 10（-8）），5个是新发现的位点（ACMSD，STK 39，MCCC 1/LAMP 3，SYT 11和CCDC 62/HIP 1 R）。另一个德系犹太人群体的GWAS也鉴定了STK 39和LAMP 3中的基因座。由于STK 39和MCCC 1/LAMP 3基因与PD之间的关联在不同人群中得到证实，我们进行了一个病例对照队列，以阐明4个单核苷酸多态性（SNP）位点（STK 39中的rs 2102808和rs3754775; MCCC 1/LAMP 3中的rs 11711441和rs 12493050）与中国汉族人群PD之间的关联。采用聚合酶链反应和直接DNA测序分析方法，对993例中国人的病例对照队列进行了检测。在rs 11711441的检测中，未分组人群、早发性PD、晚发性PD、男性PD、女性PD与相应对照组之间的等位基因和基因型频率差异均有统计学意义（p < 0.001，OR < 1）。在rs 2102808、rs3754775和rs 12493050的检测中，未分组人群、早发性PD、晚发性PD、男性PD或女性PD与相应对照组的等位基因和基因型频率均无显著性差异（p > 0.0125）。提示MCCC 1/LAMP 3基因rs 11711441等位基因G可降低中国人群PD的发病风险。其他三个SNPs的基因型频率在病例组和对照组之间没有统计学显著差异。(C)2014爱思唯尔爱尔兰有限公司版权所有。
With the completion of the Human Genome Project, GWAS have been widely used in exploring the genetic studies of complex diseases. A meta-analysis of datasets from five Parkinson's disease GWAS from the USA and Europe found 11 loci that surpassed the threshold for genome-wide significance (p < 5 x 10(-8)), and five were newly identified loci (ACMSD, STK39, MCCC1/LAMP3, SYT11 and CCDC62/HIP1R). Another GWAS of the Ashkenazi Jewish population also identified loci in STK39 and LAMP3. Because the association between the STK39 and MCCC1/LAMP3 genes and PD was confirmed in different populations, we conducted a case-control cohort to clarify the association between the four single nucleotide polymorphism (SNP) loci (rs2102808 and rs3754775 in the STK39; rs11711441 and rs12493050 in the MCCC1/LAMP3) and PD in the Chinese Han population. Polymerase chain reaction and direct DNA sequencing analyses were used to detect the four variations in a case-control cohort comprised of 993 ethnic Chinese subjects. We found that in the detection of the rs11711441, there was a significant difference between ungrouped populations, early-onset PD, late-onset PD, male PD, female PD and the corresponding control group in allele and genotype frequency (p < 0.001, OR < 1). In the detection of the rs2102808, rs3754775 and rs12493050, ungrouped populations, early-onset PD, late-onset PD, male PD or female PD with the corresponding control group showed no significant difference in allele and genotype frequency (p > 0.0125). Our findings suggested that the allele G of rs11711441 of the MCCC1/LAMP3 gene can decrease the risk of PD in Chinese population. No statistically significant difference in genotype frequency between cases and controls was observed for the other three SNPs. (C) 2014 Elsevier Ireland Ltd. All rights reserved.