Genetic association study of NLRP1, CARD, and CASP1 inflammasome genes with chronic Chagas cardiomyopathy among Trypanosoma cruzi seropositive patients in Bolivia.
Genetic association study of NLRP1, CARD, and CASP1 inflammasome genes with chronic Chagas cardiomyopathy among Trypanosoma cruzi seropositive patients in Bolivia.
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DOI：
10.1371/journal.pone.0192378
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Gilman RH
中科院分区：
文献类型：
--
作者：
Clipman SJ;Henderson-Frost J;Fu KY;Bern C;Flores J;Gilman RH
大约20-30%感染查加斯病的人患有慢性查加斯心肌病（CCC），这是该疾病最严重和最常见的表现，而其他人则保持无症状，通常不会出现查加斯特异性死亡。目前尚不清楚是什么原因导致这些不同的疾病结果，但宿主内的遗传易感性可能起着重要作用。本研究检测了62个T.来自玻利维亚的cruzi血清阳性患者（38例CCC和24例无症状对照），以揭示与CCC的关联。所有受试者均接受了完整的医学检查，包括心电图（EKG）和超声心动图。在排除3例病例和3例对照的基因型调用和质量控制过滤后，对NLRP 1、CARD和CASP 1基因中的76个直接基因型SNP进行关联分析，调整年龄、性别和人群分层。一个SNP（rs 11651270; Bonferroni校正的p = 0.036）对应于NLPR 1中的错义突变，在多次测试调整后发现具有显著性，并且在CARD 11中观察到提示性关联（rs6953573; Bonferroni校正的p = 0.060）。虽然受样本量的限制，但研究结果表明炎性小体的变化，特别是NLRP 1和CARD 11的变化，可能与CCC有关。
About 20–30% of people infected with Chagas disease present with chronic Chagas cardiomyopathy (CCC), the most serious and frequent manifestation of the disease, while others remain asymptomatic and often do not experience Chagas-specific mortality. It is not currently well understood what causes these differential disease outcomes, but a genetic predisposition within the host could play an important role. This study examined variants in the NLRP1, CARD, and CASP1 inflammasome genes among 62 T. cruzi seropositive patients from Bolivia (38 cases with CCC and 24 asymptomatic controls) to uncover associations with CCC. All subjects underwent a complete medical examination including electrocardiogram (EKG) and echocardiogram. After genotype calling and quality control filtering with exclusion of 3 cases and 3 controls, association analysis was performed across 76 directly genotyped SNPs in NLRP1, CARD, and CASP1 genes, adjusting for age, sex, and population stratification. One SNP (rs11651270; Bonferroni-corrected p = 0.036) corresponding to a missense mutation in NLPR1 was found to be significant after adjustment for multiple testing, and a suggestive association was seen in CARD11 (rs6953573; Bonferroni-corrected p = 0.060). Although limited by sample size, the study results suggest variations in the inflammasome, particularly in NLRP1 and CARD11, may be associated with CCC.
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影响因子：
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