Dataset Information

APOL1 null alleles from a rural village in India do not correlate with glomerulosclerosis.

ABSTRACT:

Background

Among African-Americans, genome wide association revealed a strong correlation between the G1 and G2 alleles of APOL1 (apolipoproteinL1, also called trypanolytic factor) and kidney diseases including focal and segmental glomerulosclerosis, HIV-associated nephropathy and hypertensive nephrosclerosis. In the prevailing hypothesis, heterozygous APOL1 G1 and G2 alleles increase resistance against Trypanosoma that cause African sleeping sickness, resulting in positive selection of these alleles, but when homozygous the G1 and G2 alleles predispose to glomerulosclerosis. While efforts are underway to screen patients for G1 and G2 alleles and to better understand "APOL1 glomerulopathy," no data prove that these APOL1 sequence variants cause glomerulosclerosis. G1 and G2 correlate best with glomerulosclerosis as recessive alleles, which suggests a loss of function mutation for which proof of causality is commonly tested with homozygous null alleles. This test cannot be performed in rodents as the APOL gene cluster evolved only in primates. However, there is a homozygous APOL1 null human being who lives in a village in rural India. This individual and his family offer a unique opportunity to test causality between APOL1 null alleles and glomerulosclerosis.

Methods and findings

We obtained clinical data, blood and urine from this APOL1 null patient and 50 related villagers. Based on measurements of blood pressure, BUN, creatinine, albuminuria, genotyping and immunoblotting, this APOL1 null individual does not have glomerulosclerosis, nor do his relatives who carry APOL1 null alleles.

Conclusions

This small study cannot provide definitive conclusions but the absence of glomerulosclerosis in this unique population is consistent with the possibility that African-American glomerulosclerosis is caused, not by loss of APOL1 function, but by other mechanisms including a subtle gain of function or by the "genetic hitchhiking" of deleterious mutations in a gene linked to APOL1 G1 and G2.

SUBMITTER: Johnstone DB

PROVIDER: S-EPMC3530541 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Publications

APOL1 null alleles from a rural village in India do not correlate with glomerulosclerosis.

Johnstone Duncan B DB Shegokar Vijay V Nihalani Deepak D Rathore Yogendra Singh YS Mallik Leena L Ashish Zare Vasant V Ikizler H Omer HO Powar Rajaram R Holzman Lawrence B LB

PloS one 20121226 12

<h4>Background</h4>Among African-Americans, genome wide association revealed a strong correlation between the G1 and G2 alleles of APOL1 (apolipoproteinL1, also called trypanolytic factor) and kidney diseases including focal and segmental glomerulosclerosis, HIV-associated nephropathy and hypertensive nephrosclerosis. In the prevailing hypothesis, heterozygous APOL1 G1 and G2 alleles increase resistance against Trypanosoma that cause African sleeping sickness, resulting in positive selection of ...[more]

PMID: 23300552

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Dataset Information

APOL1 null alleles from a rural village in India do not correlate with glomerulosclerosis.

Background

Methods and findings

Conclusions

Publications

APOL1 null alleles from a rural village in India do not correlate with glomerulosclerosis.

Similar Datasets

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