Abstract
BackgroundHigh-density lipoprotein cholesterol (HDL-C) exerts many anti-atherogenic properties including its role in reverse cholesterol transport (RCT). Scavenger receptor class B member 1 (SCARB1) plays a key role in RCT by selective uptake of HDL cholesteryl esters. We aimed to explore the genetic contribution of SCARB1 to affecting lipid levels in African Blacks from Nigeria.MethodsWe resequenced 13 exons and exon-intron boundaries of SCARB1 in 95 individuals with extreme HDL-C levels using Sanger method. Then, we genotyped 147 selected variants (78 sequence variants, 69 HapMap tagSNPs, and 2 previously reported relevant variants) in the entire sample of 788 African Blacks using either the iPLEX Gold or TaqMan methods. A total of 137 successfully genotyped variants were further evaluated for association with major lipid traits.ResultsThe initial gene-based analysis demonstrated evidence of association with HDL-C and apolipoprotein A-I (ApoA-I). The follow-up single-site analysis revealed nominal evidence of novel associations of nine common variants with HDL-C and/or ApoA-I (P < 0.05). The strongest association was between rs11057851 and HDL-C (P = 0.0043), which remained significant after controlling for multiple testing using false discovery rate. Rare variant association testing revealed a group of 23 rare variants (frequencies ≤1 %) associated with HDL-C (P = 0.0478). Haplotype analysis identified four SCARB1 regions associated with HDL-C (global P < 0.05).ConclusionsTo our knowledge, this is the first report of a comprehensive association study of SCARB1 variations with lipid traits in an African Black population. Our results showed the consistent association of SCARB1 variants with HDL-C across various association analyses, supporting the role of SCARB1 in lipoprotein-lipid regulatory mechanism.Electronic supplementary materialThe online version of this article (doi:10.1186/s12881-015-0250-6) contains supplementary material, which is available to authorized users.
Highlights
High-density lipoprotein cholesterol (HDL-C) exerts many anti-atherogenic properties including its role in reverse cholesterol transport (RCT)
Our major findings included the associations with HDL-C and apolipoprotein A-I (ApoA-I) in African Blacks, we sought to replicate four associations observed with apolipoprotein B (ApoB) levels in US Non-Hispanic White (NHW) [49] (Table 9); the association between rs11057820 and ApoB (P < 0.05) that we previously reported in US NHWs [49] was observed in African Blacks (US NHWs [G allele]: β = 0.8700, P = 0.0436; African Blacks [A allele]: β = 1.8661, P = 0.0292)
Single nucleotide polymorphism (SNP) with significant evidence with the same trait in both single-site and haplotype associations observed in each population are shown in bold SNPs with significant evidence with the different trait in single-site and haplotype associations in each population are shown in italic bold aData from Niemsiri V, et al Circ Cardiovasc Genet 2014, 7(6):838–847 (Ref [49]) b, cRefSeq of Scavenger receptor class B member 1 (SCARB1): hg19, NM_005505 (CHIP Bioinformatics) ddbSNP version 139: GRCh37.p10
Summary
High-density lipoprotein cholesterol (HDL-C) exerts many anti-atherogenic properties including its role in reverse cholesterol transport (RCT). Scavenger receptor class B member 1 (SCARB1) plays a key role in RCT by selective uptake of HDL cholesteryl esters. HDL, the smallest and densest (d = 1.063–1.21 g/mL) class of lipoprotein particles, has a variety of antiatherogenic properties [12]. One of the HDL properties to protect against CHD is mediated by reverse cholesterol transport (RCT) from peripheral tissues back to the liver [13]. Scavenger receptor class B member 1 (SCARB1, protein; SCARB1, gene) serves as a HDL-C receptor in RCT that mediates selective uptake of HDL-C cholesteryl esters (CE) by the liver and free cholesterol efflux from cells to HDL-C [14]. SCARB1 is implicated in the metabolism of apolipoprotein B (ApoB)-containing particles [15,16,17,18,19,20,21]
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