APOL1 variant modifies the HDL-kidney function relationship in populations of African ancestry

Tuesday, October 25, 2011 — Poster Session II
Noon – 2:00 p.m.	Natcher Conference Center	NHGRI	GEN/GENOM-2

Authors

• AR Bentley
• A Doumatey
• H Huang
• J Zhou
• D Shriner
• A Adeyemo
• C Rotimi

Abstract

Previously, we observed that the association between high-density cholesterol (HDL) and estimated glomerular filtration rate (eGFR, an index of kidney function) varies by ancestry: in contrast to findings among Chinese and European Americans, in West Africans (Af) and African Americans (AA), higher HDL was associated with worse eGFR. A newly identified risk variant for kidney disease (rs73885319 in apolipoprotein L 1 (APOL1)) is absent in East Asians and Europeans and likely rose to high frequency in Africa because it confers some resistance to African sleeping sickness. We investigated the role of rs73885319 in the HDL-eGFR association in 1539 AA and 283 Af. Although rs73885319 did not predict eGFR in these populations, HDL was 4-5 mg/dl higher among AA women (p=0.04) and Af (p=0.03) with the risk genotype. Among AA with the risk genotype, the negative HDL-eGFR association was nearly 6-fold larger (p=0.04; among Af, p=0.1). The discovery of an interaction between APOL1 genotype and HDL in AA suggests that genetic factors contribute to the paradoxical HDL-eGFR findings in African ancestry populations. Notably, these findings suggest that the unexplained mechanism by which the APOL1 locus affects the risk of kidney disease involves HDL.

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