發(fā)布時(shí)間：2018-08-12 13:20

【摘要】：背景:痛風(fēng)是最常見的炎性關(guān)節(jié)炎,尤其對(duì)于40歲以上的男性,是由尿酸鹽沉積在關(guān)節(jié)和結(jié)締組織引起的。痛風(fēng)的三大臨床特征是高尿酸血癥,痛風(fēng)石和關(guān)節(jié)炎。當(dāng)前的證據(jù)表明,遺傳因素參與了痛風(fēng)的進(jìn)展。為了確定遺傳因素與痛風(fēng)的潛在關(guān)聯(lián)性,本文旨在研究西藏高原漢、藏族人群中SLC2A9,WDR1,CLNK,PKD2和ABCG2基因變異與痛風(fēng)是否具有關(guān)聯(lián)性。方法:本研究從全基因組關(guān)聯(lián)分析已報(bào)道的位點(diǎn)中,共篩選出47個(gè)單核苷酸多態(tài)性位點(diǎn)(SNPs),我們采用病例-對(duì)照研究評(píng)估漢、藏族人群痛風(fēng)與SNPs的關(guān)聯(lián)性。其中痛風(fēng)患者438例(漢族139例,藏族299例),健康對(duì)照組623例(漢族309例,藏族314例),所有SNPs的基因分型使用Sequenom Mass-ARRAY技術(shù)。比值比(ORs)(校正年齡和性別)和95%置信區(qū)間(95%CIs)的估算采用非條件Logistics回歸分析,而且還用SPSS 19.0,卡方檢驗(yàn),遺傳模型分析和Haploview 4.2軟件分析痛風(fēng)與SNPs的關(guān)聯(lián)性。結(jié)果:卡方檢驗(yàn)分析發(fā)現(xiàn),在漢族人群中WDR1rs717614,CLNKrs10034180,CLNKrs16869430和ABCG2rs12505410能夠增加痛風(fēng)的易感性。在藏族人群中,CLNKrs2108878,PKD2rs2725212、rs2725210、rs2725207、rs2728132、rs2725205、rs2725203能夠增加痛風(fēng)的患病風(fēng)險(xiǎn),ABCG2rs12505410降低痛風(fēng)的患病風(fēng)險(xiǎn)。通過(guò)遺傳模型分析發(fā)現(xiàn),SLC2A9基因上rs6823877位點(diǎn)在加性模型下能降低漢族痛風(fēng)的發(fā)病風(fēng)險(xiǎn),WDR1基因上rs717614位點(diǎn)的“GG”基因型在隱性模型下能增加漢族痛風(fēng)的患病風(fēng)險(xiǎn),CLNK基因上rs10034180位點(diǎn)的“A/G-A/A”基因型在顯性模型下能增加漢族痛風(fēng)的患病風(fēng)險(xiǎn),CLNK基因上rs16869430位點(diǎn)的“C/T-T/T”基因型在顯性模型下能增加漢族痛風(fēng)的患病風(fēng)險(xiǎn),CLNK基因上rs2041216位點(diǎn)的“C/T-C/C”基因型在顯性模型下能增加漢族痛風(fēng)的患病風(fēng)險(xiǎn),CLNK基因上rs997219位點(diǎn)的“A/G-G/G”基因型在顯性模型下能增加漢族痛風(fēng)的患病風(fēng)險(xiǎn),ABCG2基因上rs12505410位點(diǎn)在加性模型下能增加漢族痛風(fēng)的患病風(fēng)險(xiǎn),ABCG2基因上rs2622626位點(diǎn)的“C/T-T/T”基因型在顯性模型下能增加漢族痛風(fēng)的患病風(fēng)險(xiǎn)。ABCG2基因上rs2231164位點(diǎn)的“T/C-C/C”基因型在顯性模型下能降低藏族痛風(fēng)的患病風(fēng)險(xiǎn)。通過(guò)Haploview 4.2分析發(fā)現(xiàn),在漢、藏族人群中4p16.1上的位點(diǎn)共構(gòu)成了4個(gè)單體域,其中SLC2A9基因上的位點(diǎn)構(gòu)成2個(gè)單體域,CLNK基因上的位點(diǎn)構(gòu)成2個(gè)單體域。4q22.1上的位點(diǎn)共構(gòu)成了3個(gè)單體域,其中PKD2基因上的位點(diǎn)構(gòu)成2個(gè)單體域,ABCG2基因上的位點(diǎn)構(gòu)成1個(gè)單體域。另外,單體型分析發(fā)現(xiàn),CLNK基因上的單體型“GTCAT”在漢族人群中能夠增加痛風(fēng)的患病風(fēng)險(xiǎn)。PKD2基因上的單體型“GGACA”和“AAAAG”在藏族人群中能夠增加痛風(fēng)的患病風(fēng)險(xiǎn),但是校正年齡和性別后,這些單體型和痛風(fēng)患病風(fēng)險(xiǎn)并不相關(guān)。結(jié)論:我們的結(jié)果結(jié)合以前的研究表明,在西藏高原漢、藏族人群中SLC2A9,WDR1,CLNK,PKD2和ABCG2這些基因變異可能會(huì)影響痛風(fēng)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.
【學(xué)位授予單位】：西藏民族大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2016
【分類號(hào)】：R589.7
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本文編號(hào)：2179175