西藏高原汉、藏人群基因多态性与痛风遗传易感性关联研究

发布时间：2018-08-12 13:20

【摘要】：背景:痛风是最常见的炎性关节炎,尤其对于40岁以上的男性,是由尿酸盐沉积在关节和结缔组织引起的。痛风的三大临床特征是高尿酸血症,痛风石和关节炎。当前的证据表明,遗传因素参与了痛风的进展。为了确定遗传因素与痛风的潜在关联性,本文旨在研究西藏高原汉、藏族人群中SLC2A9,WDR1,CLNK,PKD2和ABCG2基因变异与痛风是否具有关联性。方法:本研究从全基因组关联分析已报道的位点中,共筛选出47个单核苷酸多态性位点(SNPs),我们采用病例-对照研究评估汉、藏族人群痛风与SNPs的关联性。其中痛风患者438例(汉族139例,藏族299例),健康对照组623例(汉族309例,藏族314例),所有SNPs的基因分型使用Sequenom Mass-ARRAY技术。比值比(ORs)(校正年龄和性别)和95%置信区间(95%CIs)的估算采用非条件Logistics回归分析,而且还用SPSS 19.0,卡方检验,遗传模型分析和Haploview 4.2软件分析痛风与SNPs的关联性。结果:卡方检验分析发现,在汉族人群中WDR1rs717614,CLNKrs10034180,CLNKrs16869430和ABCG2rs12505410能够增加痛风的易感性。在藏族人群中,CLNKrs2108878,PKD2rs2725212、rs2725210、rs2725207、rs2728132、rs2725205、rs2725203能够增加痛风的患病风险,ABCG2rs12505410降低痛风的患病风险。通过遗传模型分析发现,SLC2A9基因上rs6823877位点在加性模型下能降低汉族痛风的发病风险,WDR1基因上rs717614位点的“GG”基因型在隐性模型下能增加汉族痛风的患病风险,CLNK基因上rs10034180位点的“A/G-A/A”基因型在显性模型下能增加汉族痛风的患病风险,CLNK基因上rs16869430位点的“C/T-T/T”基因型在显性模型下能增加汉族痛风的患病风险,CLNK基因上rs2041216位点的“C/T-C/C”基因型在显性模型下能增加汉族痛风的患病风险,CLNK基因上rs997219位点的“A/G-G/G”基因型在显性模型下能增加汉族痛风的患病风险,ABCG2基因上rs12505410位点在加性模型下能增加汉族痛风的患病风险,ABCG2基因上rs2622626位点的“C/T-T/T”基因型在显性模型下能增加汉族痛风的患病风险。ABCG2基因上rs2231164位点的“T/C-C/C”基因型在显性模型下能降低藏族痛风的患病风险。通过Haploview 4.2分析发现,在汉、藏族人群中4p16.1上的位点共构成了4个单体域,其中SLC2A9基因上的位点构成2个单体域,CLNK基因上的位点构成2个单体域。4q22.1上的位点共构成了3个单体域,其中PKD2基因上的位点构成2个单体域,ABCG2基因上的位点构成1个单体域。另外,单体型分析发现,CLNK基因上的单体型“GTCAT”在汉族人群中能够增加痛风的患病风险。PKD2基因上的单体型“GGACA”和“AAAAG”在藏族人群中能够增加痛风的患病风险,但是校正年龄和性别后,这些单体型和痛风患病风险并不相关。结论:我们的结果结合以前的研究表明,在西藏高原汉、藏族人群中SLC2A9,WDR1,CLNK,PKD2和ABCG2这些基因变异可能会影响痛风的易感性。
[Abstract]:Background: gout is the most common inflammatory arthritis, especially in men over 40 years old, caused by the deposition of uric acid in joints and connective tissues. The three clinical features of gout are hyperuricemia, gout stone and arthritis. Current evidence suggests that genetic factors are involved in the progression of gout. In order to determine the potential association between genetic factors and gout, this paper aims to study the association between the mutation of PKD2 and ABCG2 genes of SLC2A9 WDR1 and gout in Han and Tibetan populations in Tibet Plateau. Methods: a total of 47 single nucleotide polymorphism (SNPs),) loci were screened from the reported loci in genomic association analysis. A case-control study was conducted to evaluate the association between gout and SNPs in Han and Tibetan populations. There were 438 patients with gout (139 Han and 299 Tibetan) and 623 healthy controls (309 Han and 314 Tibetan). Sequenom Mass-ARRAY technique was used for all SNPs genotyping. The ratio of (ORs) (corrected age and sex) and 95% confidence interval (95%CIs) were estimated by non-conditional Logistics regression analysis, and the correlation between gout and SNPs was analyzed by SPSS 19.0, chi-square test, genetic model analysis and Haploview 4.2 software. Results: chi-square test showed that WDR1rs717614 CLN Krs10034180 CLN Krs16869430 and ABCG2rs12505410 could increase the susceptibility to gout in Han population. CLN Krs2108878 PKD2rs2725212rs272521010 rs2725207rs2725205rs2725205rs2725205rs2725205rs2725257203 can increase the risk of gout. ABCG2rs12505410 can decrease the risk of gout. Genetic model analysis showed that the rs6823877 locus on SLC2A9 gene could reduce the risk of gout in Han nationality under additive model. The "GG" genotype of rs717614 locus on WDR1 gene could increase the risk of gout in Han nationality under recessive model. The "A/G-A/A" genotype of the upper rs10034180 locus can increase the risk of gout in Han nationality in dominant model. The "C/T-T/T" genotype of rs16869430 locus on the rs16869430 locus of the rs16869430 gene in the dominant model can increase the risk of gout in Han nationality. C/T-C/C "genotype can increase the risk of gout in Han nationality in dominant model. The" A/G-G/G "genotype on the rs997219 locus of the rs997219 gene can increase the risk of gout in Han nationality under the dominant model. ABCG2 gene can increase the rs12505410 locus in the additive model. The "C/T-T/T" genotype of rs2622626 locus on ABCG2 gene increased the risk of gout in Han nationality. The "T/C-C/C" genotype of rs2231164 locus on ABCG2 gene decreased the risk of gout of Tibetan nationality in dominant model. By Haploview 4.2 analysis, it was found that the 4p16.1 loci in Han and Tibetan populations constituted four monomeric domains, in which the SLC2A9 loci constituted two monomeric domains, and the loci on the SLC2A9 gene constituted two monomeric domains. 4q22.1, the loci on the SLC2A9 gene constituted three monomeric domains. The loci of PKD2 gene consist of two monomeric domains and one monomer domain of ABCG2 gene. In addition, haplotype "GTCAT" on the GTCAT gene increased the risk of gout in Han population. Haplotype "GGACA" and "AAAAG" on PKD2 gene increased the risk of gout in Tibetan population. But adjusted for age and gender, these haplotypes were not associated with gout risk. Conclusion: our results combined with previous studies suggest that in Tibetan population SLC2A9 WDR1 CLNKK PKD2 and ABCG2 may affect the susceptibility to gout.
【学位授予单位】：西藏民族大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R589.7
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本文编号：2179175