Genetic association study of NLRP1, CARD, and CASP1 inflammasome genes with chronic Chagas cardiomyopathy among <i>Trypanosoma cruzi</i> seropositive patients in Bolivia

<div><p>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 <i>T</i>. <i>cruzi</i> 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.</p></div

Principle component analysis of bolivian chagas samples along with HapMap 3 populations.

<p>Each point represents one individual with different colors representing each population. Bolivian Chagas samples are coded in magenta. The HapMap populations include: ASW: African ancestry in Southwest USA; CEU: Utah residents with Northern and Western European ancestry from the CEPH collection; CHB: Han Chinese in Beijing, China; CHD: Chinese in Metropolitan Denver, Colorado; GIH: Gujarati Indians in Houston, Texas; JPT: Japanese in Tokyo, Japan; LWK: Luhya in Webuye, Kenya; MEX: Mexican ancestry in Los Angeles, California; MKK: Maasai in Kinyawa, Kenya; TSI: Tuscans in Italy; YRI: Yoruba in Ibadan, Nigeria.</p

Suggestive association results of SNPs in NLRP, CARD, CASP1 genes under an additive model unconditional logistic regression adjusted for population substructure, age, and sex.

<p>P-values reflect Bonferroni adjustment for multiple testing.</p