ABCMdb

PMID: 18199144

Slatter TL, Jones GT, Williams MJ, van Rij AM, McCormick SP
Novel rare mutations and promoter haplotypes in ABCA1 contribute to low-HDL-C levels.
Clin Genet. 2008 Feb;73(2):179-84., [PubMed]

Sentences

No. Mutations Sentence Comment

7 ABCA1 p.Arg1068His ABCA1 p.Arg2004Lys ABCA1 p.Ala2028Val ABCA1 p.Ile659Val Mutations were identified in five of the low-HDL subjects, three having novel variants (I659V, R2004K, and A2028V) and two with a previously identified variant (R1068H). Login to comment 9 ABCA1 p.Ile883Met ABCA1 p.Val825Ile The R1587K SNP was over-represented in low-HDL individuals, and the V825I and I883M SNPs over-represented in high-HDL individuals. Login to comment 20 ABCA1 p.Ile883Met ABCA1 p.Val825Ile ABCA1 p.Val771Met The C-14T promoter SNP (17), and the R1587K coding SNP (9) have been associated with low HDL-C, while the V771M (9), V825I (9, 10) and I883M (10, 18) coding SNPs have been associated with elevated HDL-C. Login to comment 41 ABCA1 p.Ile883Met ABCA1 p.Arg219Lys ABCA1 p.Val825Ile ABCA1 p.Val771Met ABCA1 p.Glu1172Asp Genotyping of ABCA1 SNPs by RFLP Fourteen SNPs including five promoter SNPs (C-564T, G-407C, G-278C, G-99C, and C-14T), one 5#-UTR SNP [-76(-75) insG], six non-synonymous coding SNPs (R219K, V771M, V825I, I883M, E1172D, and R1587K) and two 3#-UTR SNPs [A-960G -383(-381)delGTT] were genotyped in the low-, mid-, and high-HDL-C groups by restriction fragment length polymorphism (RFLP) analysis. Login to comment 55 ABCA1 p.Ile883Met ABCA1 p.Arg219Lys ABCA1 p.Val825Ile ABCA1 p.Val771Met ABCA1 p.Glu1172Asp Six of the non-synonymous variants were previously reported SNPs (R219K, V771M, V825I, I883M, E1172D and R1587K). Login to comment 56 ABCA1 p.Arg2004Lys ABCA1 p.Ala2028Val ABCA1 p.Ile659Val Three were novel mutations (I659V, R2004K and A2028V) only detected in single low-HDL individuals. Login to comment 57 ABCA1 p.Arg1068His One mutation (R1068H), detected in two low-HDL subjects, had previously been identified in an Otago family with Tangier disease (25). Login to comment 59 ABCA1 p.Arg1068His ABCA1 p.Arg2004Lys ABCA1 p.Ala2028Val ABCA1 p.Ile659Val The R1068H mutation was predicted to be Ôprobably damaging`, the R2004K mutation Ôpossibly damaging` and the I659V and A2028V mutations Ôbenign`. Login to comment 64 ABCA1 p.Ile883Met ABCA1 p.Val825Ile Two SNPs (V825I and I883M) were significantly over-represented in the high-HDL group [p ¼ 0.031 for I825 and p ¼ 0.030 for M883 (high vs low HDL-C)]. Login to comment 88 ABCA1 p.Arg1068His Of those subjects carrying ABCA1 mutations, two were heterozygous for the R1068H mutation that was previously identified in an Otago family with Tangier disease (25). Login to comment 91 ABCA1 p.Arg2004Lys ABCA1 p.Ala2028Val ABCA1 p.Ile659Val Three novel ABCA1 mutations were found in low-HDL individuals I659V, R2004K, and A2028V. Login to comment 98 ABCA1 p.Ile883Met ABCA1 p.Val825Ile Our study also identified two ABCA1 SNPs (V825I and I883M) that were over-represented in high-HDL individuals. Login to comment 105 ABCA1 p.Ile883Met ABCA1 p.Arg219Lys ABCA1 p.Val825Ile ABCA1 p.Val771Met ABCA1 p.Glu1172Asp a Coding haplotypes were derived from the following six non-synonymous SNPs (left to right): R219K (G.A), V771M (G.A), V825I (G.A), I883M (A.G), E1172D (G.C), and R1587K (G.A). Login to comment