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No evidence for association between APOL1 kidney disease risk alleles and Human African Trypanosomiasis in two Ugandan populations.

ABSTRACT: Background: Human African trypanosomiasis (HAT) manifests as an acute form caused by Trypanosoma brucei rhodesiense (Tbr) and a chronic form caused by Trypanosoma brucei gambiense (Tbg). Previous studies have suggested a host genetic role in infection outcomes, particularly for APOL1. We have undertaken candidate gene association studies (CGAS) in a Ugandan Tbr and a Tbg HAT endemic area, to determine whether polymorphisms in IL10, IL8, IL4, HLAG, TNFA, TNX4LB, IL6, IFNG, MIF, APOL1, HLAA, IL1B, IL4R, IL12B, IL12R, HP, HPR, and CFH have a role in HAT.

Methodology and results: We included 238 and 202 participants from the Busoga Tbr and Northwest Uganda Tbg endemic areas respectively. Single Nucleotide Polymorphism (SNP) genotype data were analysed in the CGAS. The study was powered to find odds ratios > 2 but association testing of the SNPs with HAT yielded no positive associations i.e. none significant after correction for multiple testing. However there was strong evidence for no association with Tbr HAT and APOL1 G2 of the size previously reported in the Kabermaido district of Uganda.

Conclusions/significance: A recent study in the Soroti and Kaberamaido focus in Central Uganda found that the APOL1 G2 allele was strongly associated with protection against Tbr HAT (odds ratio = 0.2, 95% CI: 0.07 to 0.48, p = 0.0001). However, in our study no effect of G2 on Tbr HAT was found, despite being well powered to find a similar sized effect (OR = 0.9281, 95% CI: 0.482 to 1.788, p = 0.8035). It is possible that the G2 allele is protective from Tbr in the Soroti/Kabermaido focus but not in the Iganga district of Busoga, which differ in ethnicity and infection history. Mechanisms underlying HAT infection outcome and virulence are complex and might differ between populations, and likely involve several host, parasite or even environmental factors.

SUBMITTER: Kimuda MP

PROVIDER: S-EPMC5844566 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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No evidence for association between APOL1 kidney disease risk alleles and Human African Trypanosomiasis in two Ugandan populations.

Kimuda Magambo Phillip MP Noyes Harry H Mulindwa Julius J Enyaru John J Alibu Vincent Pius VP Sidibe Issa I Mumba Ngoyi Dieuodonne D Hertz-Fowler Christiane C MacLeod Annette A Tastan Bishop Özlem Ö Matovu Enock E

PLoS neglected tropical diseases 20180222 2

<h4>Background</h4>Human African trypanosomiasis (HAT) manifests as an acute form caused by Trypanosoma brucei rhodesiense (Tbr) and a chronic form caused by Trypanosoma brucei gambiense (Tbg). Previous studies have suggested a host genetic role in infection outcomes, particularly for APOL1. We have undertaken candidate gene association studies (CGAS) in a Ugandan Tbr and a Tbg HAT endemic area, to determine whether polymorphisms in IL10, IL8, IL4, HLAG, TNFA, TNX4LB, IL6, IFNG, MIF, APOL1, HLAA ...[more]

PMID: 29470556

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Project description:Rationale & objectiveAPOL1 nephropathy risk alleles are associated with the development of chronic kidney disease (CKD) in African Americans. Although CKD is an established risk factor for mortality, associations of APOL1 risk alleles with mortality are uncertain.Study designProspective cohort.Settings & participants10,380 African American and 17,485 white American participants in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study.ExposuresAPOL1 nephropathy risk alleles.OutcomesAll-cause and cause-specific mortality.Analytical approachCox proportional hazards models were used to examine the association of APOL1 high-risk genotypes (2 risk alleles) versus APOL1 low-risk genotypes (0/1 risk allele) with all-cause and cause-specific mortality in African Americans and examine the risk for all-cause mortality in African Americans with high-risk genotypes versus African Americans with low-risk genotypes and white Americans.ResultsAPOL1 high-risk participants were younger and had a higher prevalence of albuminuria than low-risk participants. There was no statistically significant association of APOL1 high- versus low-risk genotypes with all-cause mortality in models adjusted for sociodemographic variables, comorbid conditions, and kidney function (HR, 0.88; 95% CI, 0.77-1.01). After further adjustment for genetic ancestry in a subset with available data, a statistically significant association emerged (HR, 0.81; 95% CI, 0.69-0.96). Associations differed by CKD status (Pinteraction=0.04), with African Americans with high-risk genotypes having lower risk for mortality than those with low-risk genotypes in fully adjusted models (HR, 0.78; 95% CI, 0.62-0.99) among those with CKD, but not those without CKD (HR, 0.84; 95% CI, 0.66-1.05). Compared with white Americans, African Americans with high-risk genotypes had a similar rate of mortality, whereas African Americans with low-risk genotypes had a higher rate of mortality (HR, 1.07; 95% CI, 1.00-1.14) in fully adjusted models.LimitationsLack of follow-up measures of kidney function.ConclusionsAfrican Americans with high-risk APOL1 genotypes had lower mortality than those with low-risk genotypes in multivariable-adjusted models including genetic ancestry.

Dataset Information

No evidence for association between APOL1 kidney disease risk alleles and Human African Trypanosomiasis in two Ugandan populations.

Publications

No evidence for association between APOL1 kidney disease risk alleles and Human African Trypanosomiasis in two Ugandan populations.

Similar Datasets

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