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APOL1 nephropathy risk variants are associated with altered high-density lipoprotein profiles in African Americans.

TitleAPOL1 nephropathy risk variants are associated with altered high-density lipoprotein profiles in African Americans.
Publication TypeJournal Article
Year of Publication2016
AuthorsGutiérrez, OM, Judd, SE, Irvin, MR, Zhi, D, Limdi, N, Palmer, ND, Rich, SS, Sale, MM, Freedman, BI
JournalNephrol Dial Transplant
Date Published2016 04
KeywordsAfrican Americans, Alleles, Apolipoprotein L1, Apolipoproteins, Case-Control Studies, Female, Genetic Predisposition to Disease, Genotype, Humans, Kidney Diseases, Lipoproteins, HDL, Lipoproteins, LDL, Male, Middle Aged, Polymorphism, Single Nucleotide, Risk Factors

BACKGROUND: Two independent coding variants in the apolipoprotein L1 gene (APOL1), G1 and G2, strongly associate with nephropathy in African Americans; associations with cardiovascular disease are more controversial. Although APOL1 binds plasma high-density lipoproteins (HDLs), data on APOL1 risk variant associations with HDL subfractions are sparse.METHODS: Two APOL1 G1 single nucleotide polymorphisms and the G2 insertion/deletion polymorphism were genotyped in 2010 Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study participants with nuclear magnetic resonance spectroscopy-based lipoprotein subfraction measurements. Linear regression was used to model associations between numbers of APOL1 G1/G2 risk variants and HDL subfractions, adjusting for demographic, clinical and ancestral covariates.RESULTS: Female sex and higher percentage of African ancestry were positively associated with the number of APOL1 G1/G2 risk alleles. In the unadjusted analysis, mean (standard error) small HDL concentrations (μmol/L) for participants with zero, one and two G1/G2 risk alleles were 19.0 (0.2), 19.7 (0.2) and 19.9 (0.4), respectively (P = 0.02). Adjustment for age, sex, diabetes and African ancestry did not change the results but strengthened the statistical significance (P = 0.004). No significant differences in large or medium HDL, very low-density lipoprotein or low-density lipoprotein particle concentrations were observed by APOL1 genotype.CONCLUSIONS: Greater numbers of APOL1 G1/G2 risk alleles were associated with higher small HDL particle concentrations in African Americans. These results may suggest novel areas of investigation to uncover reasons for the association between APOL1 risk variants with adverse outcomes in African Americans.

Alternate JournalNephrol. Dial. Transplant.
PubMed ID26152403
PubMed Central IDPMC4805128
Grant ListR01 DK084149 / DK / NIDDK NIH HHS / United States
R01 DK070941 / DK / NIDDK NIH HHS / United States
P30 DK079626 / DK / NIDDK NIH HHS / United States
K24 HL133373 / HL / NHLBI NIH HHS / United States
U01 NS041588 / NS / NINDS NIH HHS / United States
R01 NS080850 / NS / NINDS NIH HHS / United States
R03 DK095005 / DK / NIDDK NIH HHS / United States