African Americans are more susceptible than white Americans to certain forms of kidney disease, such as focal segmental glomerulosclerosis (FSGS) and hypertension-induced end-stage renal disease (ESRD). Previous studies identified an association between risk of kidney disease in these individuals and genetic variation at a locus near MYH9 on chromosome 22; however, causal mutations in MYH9 have not been identified and recent findings led Pollak and colleagues to expand their search. “In the course of our research, we did a genome-wide association scan of patients with FSGS, which made us suspect that the major gene accounting for the high rate of FSGS in black individuals could be located in a larger genomic region than originally suspected”, says Pollak.
To investigate whether variations in this expanded chromosomal region may be responsible for the increased association of renal disease in black individuals, Pollak and colleagues analyzed sequence data from the 1,000 Genomes Project to identify polymorphisms that markedly differed in frequency between Africans and Europeans. They then compared sequence variations between 205 African-American individuals with biopsy-proven FSGS and 180 African-American individuals with no evidence of renal disease. The researchers identified two variations in the APOL1 gene—termed G1 and G2—that correlated with disease. “Comparing subjects with zero or one risk allele to subjects with two risk alleles provided an odds ratio for FSGS of 10.5 ([95%] CI 6.0–18.4)”, say the researchers.
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