ABCMdb

PMID: 23136402

Bochem AE, van Wijk DF, Holleboom AG, Duivenvoorden R, Motazacker MM, Dallinga-Thie GM, de Groot E, Kastelein JJ, Nederveen AJ, Hovingh GK, Stroes ES
ABCA1 mutation carriers with low high-density lipoprotein cholesterol are characterized by a larger atherosclerotic burden.
Eur Heart J. 2013 Jan;34(4):286-91. doi: 10.1093/eurheartj/ehs376. Epub 2012 Nov 7., [PubMed]

Sentences

No. Mutations Sentence Comment

69 ABCA1 p.Asn1800His ABCA1 p.Thr929Ile ABCA1 p.Arg587Trp ABCA1 p.Ser930Phe ABCA1 p.Asp571Gly ABCA1 p.Asn935Ser ABCA1 p.Leu1056Pro ABCA1 p.Ser824Leu ABCA1 p.Arg579Gln Subjects were carriers of the following mutations: c.6401+2T.C, p.Ser930Phe, p.Ser824Leu, p.Arg587Trp, p.Thr929Ile, p.Asn935Ser, c.3535+1G.C, p.Asp571Gly, p.Asn1800his, p.Leu1056Pro, p.Gln1038Ter, c.1195-1G.C, p.Arg579Gln, and p.Phe1760Valfs*21. Login to comment 78 ABCA1 p.Asn1800His ABCA1 p.Thr929Ile ABCA1 p.Arg587Trp ABCA1 p.Leu1056Pro Five of these mutations have already been shown to have a significant impact on ABCA1 function (p.Asn1800his,27 p.Thr929Ile,27 p.Arg587Trp,28,29 p.Leu1056Pro,21 and p.Phe1760Valfs*21.30 ). Login to comment 79 ABCA1 p.Ser930Phe ABCA1 p.Asp571Gly ABCA1 p.Asn935Ser ABCA1 p.Ser824Leu ABCA1 p.Arg579Gln The efflux capacity of the remaining nine mutations: p.Asn935Ser, c.3535+1G.C, p.Ser824Leu, p.Ser930Phe, p.Gln1038Ter, c.1195-1G.C, c.6401+2T.C, p.Asp571Gly, and p.Arg579Gln are listed in Figure 1. Login to comment 81 ABCA1 p.Cys1477Arg ABCA1 p.Val771Met ABCA1 p.Arg579Gln Efflux measured in fibroblasts from a heterozygous p.Cys1477Arg carrier was used as a positive control since the efflux capacity has consistently been shown to be impaired.19,27 One patient compound heterozygous for mutation p.Arg579Gln and p.Val771Met was included. Login to comment 82 ABCA1 p.Val771Met ABCA1 p.Val771Met ABCA1 p.Arg579Gln ABCA1 p.Arg579Gln In the view of contradictory statements on functionality of mutation p.Val771Met,31 we assumed that the major part of the efflux impairment of the p.Arg579Gln and p.Val771Met combination is attributable to p.Arg579Gln. Login to comment 115 ABCA1 p.Lys776Asn An alternative approach is the assessment of effects of genetic variation in ABCA1 using a Mendelian randomization approach as performed by Frikke-Schmidt et al.42 In line with our results, they report that in a prospective cohort comprising 9000 individuals, heterozygosity for the ABCA1 mutation p.Lys776Asn led to a two-to-three-fold higher risk of ischaemic heart disease. Login to comment