UMOD Genotype and Determinants of Urinary Uromodulin in African Populations

Figures

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  Figure 1. Distribution of the UMOD/PDILT SNPs in African and European populations from the 1000 Genomes Project, the African-PREDICT and the PURE cohorts. (a) Genotype distribution of rs4293393 (UMOD), rs12917707 (UMOD), and rs12446492 (PDILT) in the African samples from the 1000 Genomes Project, compared to the global and European sample prevalence. (b) Genotype distribution of rs4293393, rs12917707, and rs12446492 in Black and White adults from the African-PREDICT and PURE studies. Blue sections represent the frequencies of “CKD risk” alleles and red sections the frequencies of “CKD protective” alleles. Populations represented in the European ancestry (n = 503) group of the 1000 Genomes Project included: Utah residents from North and West Europe CEU (n = 99), Toscani in Italia TSI (n = 107), Finnish in Finland FIN (n = 99), British in England and Scotland GBR (n = 91), and Iberian population in Spain IBS (n = 107). The African superpopulation is composed of the following populations: African Caribbean in Barbados ACB (n = 96), Gambian in Western Divisions GWD in the Gambia (n = 113), Luhya in Webuye, Kenya LWK (n = 99), Esan in Nigeria ESN (n = 99), Yoruba in Ibadan, Nigeria YRI (n =…

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  Figure 2. Linkage disequilibrium (LD) and haplotype analysis of the UMOD-PDILT locus. (a) LD map of the UMOD-PDILT locus based on 1000 Genomes Project summary data for African (n = 661) and European (n = 502) populations. D’ values are indicated, and the 3 SNPs of interest highlighted on the graph with their LD statistics (D’ and r2) shown below. Graph generated using Haploview 4.2. (b) LD estimates (D’ and r2) for 3 SNPs of interest in Whites (n = 535) and Blacks (n = 543) from the African-PREDICT cohort. (c) Haplotype frequency estimates in Whites and Blacks from the African-PREDICT cohort. Only the 3 most common haplotypes are shown. The grey star shows a recombination event between rs4293393 and rs12917707 that is frequent in blacks and virtually absent in whites. MAF, minor allele frequencies.

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  Figure 3. Effects of the UMOD-PDILT genotype on urinary uromodulin levels. Comparison of urinary uromodulin/creatinine levels according to genotypes at rs4293393 (UMOD), rs12917707 (UMOD) and rs12446492 (PDILT) in ● Black and ○ White adults from the African-PREDICT study; and ● Black adults from the PURE study. Data presented as geometric mean and 95th percentile. Bonferroni corrected P values shown for Welch’s analysis of variance comparing uromodulin and uromodulin/creatinine across groups. An interaction term SNP∗ethnicity is reported as p interaction for all 3 SNPs. SNP, single-nucleotide polymorphism.

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  Figure 4. Determinants of urinary uromodulin in the African-PREDICT study. Multiple regression analyses in the total African-PREDICT study population and split according to ethnicity. Continuous variables were standardized by creating z-variables, which were included into multiple regression models for this forest plot. BMI, body mass index; UACR, urinary albumin-creatinine ratio.