ABCMdb

ABCA1 p.Trp590Leu

ClinVar:	c.1769G>C , p.Trp590Ser D , Pathogenic
Predicted by SNAP2:	A: D (71%), C: D (71%), D: D (85%), E: D (80%), F: D (71%), G: D (80%), H: D (85%), I: D (75%), K: D (80%), L: D (80%), M: D (80%), N: D (75%), P: D (85%), Q: D (75%), R: D (75%), S: D (75%), T: D (71%), V: D (75%), Y: D (66%),
Predicted by PROVEAN:	A: D, C: D, D: D, E: D, F: D, G: D, H: D, I: D, K: D, L: D, M: D, N: D, P: D, Q: D, R: D, S: D, T: D, V: D, Y: D,

[switch to compact view]
Comments [show]

None has been submitted yet.

Publications
[hide] Genetic etiology of isolated low HDL syndrome: inc... Arterioscler Thromb Vasc Biol. 2007 May;27(5):1139-45. Epub 2007 Feb 15. Kiss RS, Kavaslar N, Okuhira K, Freeman MW, Walter S, Milne RW, McPherson R, Marcel YL
Genetic etiology of isolated low HDL syndrome: incidence and heterogeneity of efflux defects.
Arterioscler Thromb Vasc Biol. 2007 May;27(5):1139-45. Epub 2007 Feb 15., [PMID:17303779]

Abstract [show]
OBJECTIVE: We have used a multitiered approach to identify genetic and cellular contributors to high-density lipoprotein (HDL) deficiency in 124 human subjects. METHODS AND RESULTS: We resequenced 4 candidate genes for HDL regulation and identified several functional nonsynonymous mutations including 2 in apolipoprotein A-I (APOA1), 4 in lecithin:cholesterol acyltransferase (LCAT), 1 in phospholipid transfer protein (PLTP), and 7 in the ATP-binding cassette transporter ABCA1, leaving 88% (110/124) of HDL deficient subjects without a genetic diagnosis. Cholesterol efflux assays performed using cholesterol-loaded monocyte-derived macrophages from the 124 low HDL subjects and 48 control subjects revealed that 33% (41/124) of low HDL subjects had low efflux, despite the fact that the majority of these subjects (34/41) were not carriers of dysfunctional ABCA1 alleles. In contrast, only 2% of control subjects presented with low efflux (1/48). In 3 families without ABCA1 mutations, efflux defects were found to cosegregate with low HDL. CONCLUSIONS: Efflux defects are frequent in low HDL syndromes, but the majority of HDL deficient subjects with cellular cholesterol efflux defects do not harbor ABCA1 mutations, suggesting that novel pathways contribute to this phenotype.

Comments [show]

None has been submitted yet.

Sentences [show]
No. Sentence Comment
47 In ABCA1, a total of 19 nonsynonymous coding sequence variants; some of these we reported previously.22 Of these, 9 sequence variants were common polymorphisms (ie, reported in the literature as common or of similar prevalence in control subjects): P85L, P85A, R219K, V399A, V771M, V825I, I883M, E1172D, R1587K.14,32-35 Another 5 sequence variants, identified here, were previously reported to be disease causing: W590L (reported as W590S)14; C1477F (reported as C1477R)13; S1731C (only found in French-Canadian populations)36; N1800H32; and 1851X.37 Five sequence variants were novel: K199F, H551D, R965C, E1386Q, and D1706N. Login to comment
49 Eight subjects with sequence variants in ABCA1 had defective cholesterol efflux (measured in repeated assays cholesterol-loaded monocyte-derived macrophage [MDMs]), and these ABCA1 sequence variants were tested in an in vitro expression system for cholesterol efflux activity.38 ABCA1 proteins containing the sequence variants W590L, C1477F, D1706N, S1731C, or N1800H were all found to have significantly impaired cholesterol efflux, whereas the H551D and E1386Q variants had very minor, if any, effects on cholesterol transport (Figure 1A). Login to comment
88 of Subjects Functional Mutations (All Heterozygous) Percentage of Total Population ApoA-I 2 33X, ⌬K182 2 ABCA1 7 H551D, W590L, C1477F, D1706N, S1731C, N1800H, 1851X 6 LCAT 4 W61X, G104S, N131D, S208T 3 PLTP 1 R459Q 1 Unknown 88 Total no. Login to comment
42 In ABCA1, a total of 19 nonsynonymous coding sequence variants; some of these we reported previously.22 Of these, 9 sequence variants were common polymorphisms (ie, reported in the literature as common or of similar prevalence in control subjects): P85L, P85A, R219K, V399A, V771M, V825I, I883M, E1172D, R1587K.14,32-35 Another 5 sequence variants, identified here, were previously reported to be disease causing: W590L (reported as W590S)14; C1477F (reported as C1477R)13; S1731C (only found in French-Canadian populations)36; N1800H32; and 1851X.37 Five sequence variants were novel: K199F, H551D, R965C, E1386Q, and D1706N. Login to comment
44 Eight subjects with sequence variants in ABCA1 had defective cholesterol efflux (measured in repeated assays cholesterol-loaded monocyte-derived macrophage [MDMs]), and these ABCA1 sequence variants were tested in an in vitro expression system for cholesterol efflux activity.38 ABCA1 proteins containing the sequence variants W590L, C1477F, D1706N, S1731C, or N1800H were all found to have significantly impaired cholesterol efflux, whereas the H551D and E1386Q variants had very minor, if any, effects on cholesterol transport (Figure 1A). Login to comment
83 of Subjects Functional Mutations (All Heterozygous) Percentage of Total Population ApoA-I 2 33X, èc;K182 2 ABCA1 7 H551D, W590L, C1477F, D1706N, S1731C, N1800H, 1851X 6 LCAT 4 W61X, G104S, N131D, S208T 3 PLTP 1 R459Q 1 Unknown 88 Total no. Login to comment

[hide] Do mutations causing low HDL-C promote increased c... Clin Chim Acta. 2007 Feb;377(1-2):273-5. Epub 2006 Oct 7. Miller M, Rhyne J, Hong SH, Friel G, Dolinar C, Riley W
Do mutations causing low HDL-C promote increased carotid intima-media thickness?
Clin Chim Acta. 2007 Feb;377(1-2):273-5. Epub 2006 Oct 7., [PMID:17113061]

Abstract [show]
BACKGROUND: Although observational data support an inverse relationship between high-density lipoprotein (HDL) cholesterol and coronary heart disease (CHD), genetic HDL deficiency states often do not correlate with premature CHD. METHODS: Carotid intima-media thickness (cIMT) measurements were obtained in cases comprising 10 different mutations in LCAT, ABCA1 and APOA1 to further evaluate the relationship between low HDL resulting from genetic variation and early atherosclerosis. RESULTS: In a 1:2 case-control study of sex and age-related (+/-5 y) subjects (n=114), cIMT was nearly identical between cases (0.66+/-0.17 cm) and controls (0.65+/-0.18 cm) despite significantly lower HDL cholesterol (0.67 vs. 1.58 mmol/l) and apolipoprotein A-I levels (96.7 vs. 151.4 mg/dl) (P<0.05) CONCLUSIONS: Genetic variants identified in the present study may be insufficient to promote early carotid atherosclerosis.

Comments [show]

None has been submitted yet.

Sentences [show]
No. Sentence Comment
37 These data extend previous observations where increased cIMT was not associated with the ABCA1 variant, W590L [14]. Login to comment

[hide] Accurate prediction of the functional significance... PLoS Genet. 2005 Dec;1(6):e83. Epub 2005 Dec 30. Brunham LR, Singaraja RR, Pape TD, Kejariwal A, Thomas PD, Hayden MR
Accurate prediction of the functional significance of single nucleotide polymorphisms and mutations in the ABCA1 gene.
PLoS Genet. 2005 Dec;1(6):e83. Epub 2005 Dec 30., [PMID:16429166]

Abstract [show]
The human genome contains an estimated 100,000 to 300,000 DNA variants that alter an amino acid in an encoded protein. However, our ability to predict which of these variants are functionally significant is limited. We used a bioinformatics approach to define the functional significance of genetic variation in the ABCA1 gene, a cholesterol transporter crucial for the metabolism of high density lipoprotein cholesterol. To predict the functional consequence of each coding single nucleotide polymorphism and mutation in this gene, we calculated a substitution position-specific evolutionary conservation score for each variant, which considers site-specific variation among evolutionarily related proteins. To test the bioinformatics predictions experimentally, we evaluated the biochemical consequence of these sequence variants by examining the ability of cell lines stably transfected with the ABCA1 alleles to elicit cholesterol efflux. Our bioinformatics approach correctly predicted the functional impact of greater than 94% of the naturally occurring variants we assessed. The bioinformatics predictions were significantly correlated with the degree of functional impairment of ABCA1 mutations (r2 = 0.62, p = 0.0008). These results have allowed us to define the impact of genetic variation on ABCA1 function and to suggest that the in silico evolutionary approach we used may be a useful tool in general for predicting the effects of DNA variation on gene function. In addition, our data suggest that considering patterns of positive selection, along with patterns of negative selection such as evolutionary conservation, may improve our ability to predict the functional effects of amino acid variation.

Comments [show]

None has been submitted yet.

Sentences [show]
No. Sentence Comment
48 This SNP has been reported to be associated with decreased HDL cholesterol and increased severity of atherosclerosis in Table 1. subPSEC Scores and Probability of Functional Impairment (Pdeleterious) for ABCA1 Mutations and SNPs Mutations SNPs Variant SubPSEC Pdeleterious Variant subPSEC Pdeleterious P85L À4.62 0.83 R219K À0.57 0.08 H160F À2.79 0.45 V399A À2.26 0.32 R230C À4.27 0.78 V771M À2.86 0.46 A255T À1.81 0.23 T774P À1.99 0.27 E284K À2.34 0.34 K776N À3.53 0.63 Y482C À4.21 0.77 V825I À1.06 0.13 R587W À6.04 0.95 I883M À1.38 0.17 W590S À5.19 0.9 E1172D À1.96 0.26 W590L À4.48 0.82 R1587K À0.58 0.08 Q597R À7.15 0.98 S1731C À4.21 0.77 T929I À4.29 0.78 N935H À8.54 1 N935S À7.53 0.99 A937V À6.6 0.97 A1046D À7.52 0.99 M1091T À3.56 0.64 D1099Y À6.09 0.96 D1289N À2.48 0.37 L1379F À3.81 0.69 C1477R À5.44 0.92 S1506L À5.17 0.9 N1611D À5.69 0.94 R1680W À6.02 0.95 V1704D À3.21 0.55 N1800H À4.23 0.77 R1901S À5.06 0.89 F2009S À2.73 0.43 R2081W À8.08 0.99 P2150L À2.88 0.47 Q2196H À2.74 0.43 DOI: 10.1371/journal.pgen.0010083.t001 PLoS Genetics | www.plosgenetics.org December 2005 | Volume 1 | Issue 6 | e83 0740 Accurate Prediction of ABCA1 Variants Synopsis A major goal of human genetics research is to understand how genetic variation leads to differences in the function of genes. Login to comment
110 DOI: 10.1371/journal.pgen.0010083.g003 Table 3. subPSEC Scores for ABCA1 Variants Described in a Cohort of Individuals with Low HDL Cholesterol from the General Population Variant subPSEC Score Macrophage Efflux PolyPhen D1706N À6.57 0.38a Possibly damaging C1477F À5.55 0.34a Probably damaging W590S À5.19 - Probably damaging H551D À4.99 0.32a Probably damaging P85L À4.62 0.8 Probably damaging W590L À4.48 0.31a Probably damaging N1800H À4.23 0.27a Possibly damaging R965C À4.22 0.59 Probably damaging S1731C À4.21 0.28a Possibly damaging A1670T À4.2 - Possibly damaging K401Q À4.2 - Benign T459P À4.11 0.28a Possibly damaging R638Q À4.08 - Possibly damaging L1026P À3.86 0.25a Benign T2073A À3.84 0.28a Possibly damaging E815G À3.53 - Probably damaging R1615Q À3.45 - Possibly damaging S1181F À3.44 - Possibly damaging R306H À3.31 - Benign E1386Q À2.44 0.51 Benign S1376G À2.19 - Benign R1341T À2.09 - Possibly damaging D2243E À1.6 - Benign P248A À0.18 - Benign a Efflux value is 2 SDs or more below control levels of 0.52 6 0.07. Login to comment

[hide] Inherited disorders of HDL metabolism and atherosc... Curr Opin Lipidol. 2005 Apr;16(2):139-45. Hovingh GK, de Groot E, van der Steeg W, Boekholdt SM, Hutten BA, Kuivenhoven JA, Kastelein JJ
Inherited disorders of HDL metabolism and atherosclerosis.
Curr Opin Lipidol. 2005 Apr;16(2):139-45., [PMID:15767853]

Abstract [show]
PURPOSE OF REVIEW: Genetic disorders of HDL metabolism are rare and, as a result, the assessment of atherosclerosis risk in individuals suffering from these disorders has been difficult. Ultrasound imaging of carotid arteries has provided a tool to assess the risk in hereditary hypo and hyperalphalipoproteinemia. This review gives a comprehensive summary. RECENT FINDINGS: Epidemiological studies have unequivocally shown that HDL cholesterol levels are inversely related to coronary artery disease risk, but the literature concerning genetic disorders of HDL metabolism provides less convincing information. Fortuitously, we were able to directly compare carotid intima media thickness data of substantial numbers of individuals with mutations in either apolipoprotein A-I (apoA-I), ATP binding cassette AI (ABCA1), lecithin: cholesterol acyltransferase (LCAT) or cholesteryl ester transfer protein. These data show that carriers of an apoA-I mutation exhibit the most pronounced accelerated atherosclerosis compared with those carrying mutations in ABCA1 and LCAT. Heterozygosity for a non-sense mutation in cholesteryl ester transfer protein did, by contrast, not distinguish carriers from controls in terms of intima media thickness progression. We will discuss these results in the context of the current literature. SUMMARY: Intima media thickness studies have provided evidence that hypoalphalipoproteinemia due to mutations in apoA-I, ABCA1, and LCAT is associated with increased progression of atherosclerosis. In contrast, hyperalphalipoproteinemia as a result of loss of cholesteryl ester transfer protein function is associated with unaltered atherosclerosis progression compared with family controls. This insight is of interest, since it can assist in the prioritizing of antiatherogenic therapy by increasing HDL cholesterol levels.

Comments [show]

None has been submitted yet.

Sentences [show]
No. Sentence Comment
82 In contrast, no effects on carotid IMT were observed in carriers of another ABCA1 mutation (W590L) [37]. Login to comment
85 In addition, HDL-c levels were below 1.0 mmol/l in three of the five ABCA1 mutation carriers and in two of the 10 noncarriers, indicating that the W590L mutation suffers from low penetrance. Login to comment

[hide] Screening for functional sequence variations and m... Atherosclerosis. 2004 Aug;175(2):269-79. Probst MC, Thumann H, Aslanidis C, Langmann T, Buechler C, Patsch W, Baralle FE, Dallinga-Thie GM, Geisel J, Keller C, Menys VC, Schmitz G
Screening for functional sequence variations and mutations in ABCA1.
Atherosclerosis. 2004 Aug;175(2):269-79., [PMID:15262183]

Abstract [show]
Mutations in the ATP-binding cassette 1 transporter gene (ABCA1) are responsible for the genetic HDL-deficiency syndromes, which are characterized by severely diminished plasma HDL-C levels and a predisposition to cardiovascular disease and splenomegaly. The ABCA1 gene contains 50 exons and codes for a 2261-amino acid long membrane protein that facilitates phospholipid and cholesterol transport. Several mutations have been identified so far as responsible either for Tangier disease or for reduced HDL levels. We have selectively looked for additional polymorphisms in functionally relevant regions of the gene in cohorts constituted of individuals with altered HDL levels as well as healthy blood donors and octogenarians, and screened for mutations in the complete coding region of selected individuals with extremely aberrant HDL levels. In the promoter region, which is important for regulation of gene expression, we have identified several polymorphisms including one VNTR polymorphism, located at a putative ZNF202 binding site, which displayed different binding of ZNF202 in an electromobility shift assay. Three novel SNPs were discovered in the promoter region (G1047C, C1152T and C1440T). The prevalence of exchange G1047C (G-395C) was found significantly increased in probands with low HDL compared to probands with high HDL. Exchanges C1152T (C-290T) and C1440T (C-7T) were significantly more frequent in the cohort with low HDL compared to healthy blood donors and octogenarians. In the C-terminal part of ABCA1, known to interact with other proteins, two novel sequence variations (F2163S and V2244I) have been found in one phenotype related to cardiovascular disease, but none in the aforementioned cohorts. In one individual with extremely high HDL levels, the V771M polymorphism was found in a homozygous state. In patients with HDL deficiency, three novel mutations have been identified (W590L, W840R and R1068C). To facilitate further research in ABCA1 sequence variations and expand our understanding of their effects, we are introducing a webpage archive (http://www.abca1-mutants.all.at) containing all sequence variations reported in ABCA1 so far. This webpage provides a more recent and detailed summary of sequence variations and mutations in ABCA1 than existing databases and should also be of interest for molecular diagnosis of ABCA1-related HDL deficiency.

Comments [show]

None has been submitted yet.

Sentences [show]
No. Sentence Comment
10 In patients with HDL deficiency, three novel mutations have been identified (W590L, W840R and R1068C). Login to comment
123 These Table 1 Primers and probes for TaqMan analysis of novel polymorphisms in the coding region of ABCA1 W590L (G2082C) TM-W590L-f 5 -AGC TGA CCC CTT TGA GGA CAT-3 TM-W590L-r 5 -CTC CAC CAC ATC CTG CAA GTA G-3 TM-W590-vic 5 -VIC-CCC CCC ¯ AGA CGT A-MGB-NFQ-3 TM-L590-fam 5 -FAM-CCC CCG ¯ AGA CGT A-MGB-NFQ-3 V771M (G2624A) TM-V771M-f 5 -GGC ATC ATC TAC TTC ACG CTG TA-3 TM-V771M-r 5 -CAG AGG TAC TCA CAG CGA AGA TCT T-3 TM-V771-vic 5 -FAM-TGT GAA GCC CAC ¯ GTA G-MGB-NFQ-3 TM-M771-fam 5 -VIC-TGA AGC CCA T ¯ GT AGT C-MGB-NFQ-3 W840R (T2831A) TM-W840R-f 5 -GCT GTT TGA CAC CTT CCT CTA TGG-3 TM-W840R-r 5 -TGT ACC TGG AAA GAC AGC CTC AA-3 TM-W840-vic 5 -VIC-TGT ACC A ¯ GG TCA TCA C-MGB-NFQ-3 TM-R840-fam 5 -FAM-TGT ACC T ¯ GG TCA TCA C-MGB-NFQ-3 P2150L (C6762T) TM-P2150L-f 5 -TTC AGG TTT GGA GAT GGT TAT ACA ATA G-3 TM-P2150L-r 5 -GAA ATG CAA GTC CAA AGA AAT CCT-3 TM-P2150-vic 5 -VIC-CAA CCC ¯ GGA CCT GA-MGB-NFQ-3 TM-L2150-fam 5 -FAM-CAA CCT ¯ GGA CCT GAA-MGB-NFQ-3 F2163S (T6801C) TM-F2163S-f 5 -AAG CCT GTC CAG GAT TTC TTT G-3 TM-F2163S-r 5 -CAT GTT CCG GTG TTT CTC TTT TAG-3 TM-F2163-vic 5 -VIC-CCA GGA A ¯ AT GCA AGT C-MGB-NFQ-3 TM-S2163-fam 5 -FAM-CAG GAG ¯ ATG CAA GTC-MGB-NFQ-3 V2244I (G7043A) TM-V2244I-f 5 -ATG ATG ACC ACT TAA AAG ACC TCT CA-3 TM-V2244I-r 5 -GCT TTC TTT CAC TTT CTC ATC CTG TAG-3 TM-V2244-vic 5 -VIC-TGG ACG ¯ TTG CAG TTC-MGB-NFQ-3 TM-I2244-fam 5 -FAM-AGT AGT GGA CA ¯ T TGC-MGB-NFQ-3 Positions of sequence variations refer to accession number NM005502. Login to comment
186 In the 61-year-old male (patient C), we found the novel mutation G98481T in a heterozygous state, which results in amino acid exchange W590L. Login to comment
192 In addition, patient D was heterozygous for a novel sequence variation in exon 22, Table 5 Sequence variations found in ABCA1 and phenotypes of patients Exon Amino acid Nucleotide Position in DNA (AF275948) Position in mRNA (NM005502) Found in patient with 14 W590L TG ¯ G → TC ¯ G 98481 2082 HDL deficiency (C) 16 V771M G ¯ TG → A ¯ TG 102555 2624 Increased HDL (A) 17 W840R T ¯ GG → A ¯ GG 103822 2831 HDL deficiency (B) 22 R1068C C ¯ GC → T ¯ GC 109904 3515 HDL deficiency (D) 49 F2163S TT ¯ T → TC ¯ T 143483 6801 Low HDL and G6PD deficiency (E) 50 V2244I G ¯ TT → A ¯ TT 144665 7043 A C ABC B S A N ABC B S 44 23 703 681 718 740 769 747 774-794 822 842 1368 1346 1655 1677 1724 1702 1737 1759 1790 1768 1848 1870 642 660 W590L R1068C F2163S P2150L V2244I V771M W840R Fig. 4. Login to comment
241 In the probands with HDL deficiency (patients B, C and D), we have identified three novel sequence variations: W840R, W590L and R1068C. Login to comment
244 It can also be assumed that amino acid exchange W590L, found in patient C, is a mutation causing a defect ABCA1 protein product. Login to comment
245 This is supported by the fact that a mutation in the same codon was shown to cause Tangier disease (W590S) [7], but since the patient is only heterozygous for W590L, it remains unclear what additional mutation in ABCA1 causes the patients analphalipoproteinemia. Login to comment

[hide] Lack of association between increased carotid inti... Clin Chem. 2002 Nov;48(11):2066-70. Hong SH, Riley W, Rhyne J, Friel G, Miller M
Lack of association between increased carotid intima-media thickening and decreased HDL-cholesterol in a family with a novel ABCA1 variant, G2265T.
Clin Chem. 2002 Nov;48(11):2066-70., [PMID:12407001]

Abstract [show]
Low HDL-cholesterol (HDL-C) concentrations are inversely correlated with cardiovascular disease, and previous studies have demonstrated that variants in the ATP-binding cassette transporter, ABCA1, are responsible for a proportion of HDL-C deficiency states. We identified a novel variant in ABCA1 in a kindred with decreased HDL-C. This variant was not identified in >200 chromosomes of healthy individuals. The proband, a heterozygote for G2265T, developed premature coronary artery disease. In addition to low HDL-C, six biological family members heterozygous for the ABCA1 variant exhibited low HDL-C concentrations compared with unaffected family members (0.83 +/- 0.32 vs 1.33 +/- 0.36 mmol/L; P = 0.009). Despite the decreased HDL-C, carotid artery B-mode ultrasound studies failed to reveal increased intima-media thickening in affected individuals compared with age- and sex-matched controls. Although these data extend previous observations that a single defective ABCA1 allele may lead to decreased HDL-C, associated evidence of early atherosclerosis was not confirmed.

Comments [show]

None has been submitted yet.

Sentences [show]
No. Sentence Comment
51 The affected individuals in the kindred were heterozygous for a G2265T substitution (Fig. 2, arrow) with predicted conversion of Trp to Leu (W590L). Login to comment
55 Pedigree of a kindred showing HDL-C segregation of W590L mutation. Login to comment
62 Significant differences between (ϩ) and (-) individuals for the W590L mutation were noted for HDL-C (P ϭ 0.009) and apoA-I (P ϭ 0.036). Login to comment
75 Individuala Sex Age, years TC,b mmol/L TG, mmol/L HDL-C, mmol/L LDL-C, mmol/L apoA-I, g/L apoB, g/L I-2 (-) F 88 5.43 3.28 1.40 3.39 1.67 1.10 I-3 (؉) M 81 4.63 2.20 1.06 3.13 1.21 0.95 II-1 (-) M 48 4.88 4.34 1.14 2.87 1.32 1.00 II-2 (-) F 47 5.53 3.54 1.65 3.18 2.00 1.11 II-3 (؉) M 52 3.10 2.97 0.34 2.17 0.49 0.93 II-4 (-) F 54 3.95 1.63 1.65 1.96 1.54 0.60 II-5 (؉) M 57 5.19 2.38 1.14 3.59 1.39 1.18 II-6 (-) F 54 3.67 1.24 1.14 2.17 1.18 0.64 II-7 (-) M 54 7.13 4.91 1.94 4.21 2.05 1.26 II-8 (؉) F 40 3.80 2.45 0.88 2.43 1.06 0.86 III-1 (-) F 19 4.16 2.48 0.96 2.71 1.01 0.79 III-2 (-) M 27 3.10 2.43 1.27 1.34 1.51 0.54 III-3 (؉) M 31 3.70 2.74 0.54 2.61 0.85 0.98 III-4 (؉) F 28 3.80 2.35 1.03 2.30 1.29 0.80 III-5 (-) F 33 3.98 1.52 1.40 2.27 1.34 0.68 III-6 (-) F 19 3.95 2.74 0.96 2.45 1.10 0.75 III-7 (-) F 27 5.37 2.07 1.96 2.89 1.90 0.93 III-8 (-) M 10 3.64 2.25 1.01 2.20 1.15 0.77 III-9 (-) M 13 3.70 1.60 1.24 2.14 1.24 0.68 III-10 (-) F 17 3.23 3.75 0.88 1.60 1.09 0.62 Mean Ϯ SD (ϩ), n ϭ 6 41.60 Ϯ 12.70 4.04 Ϯ 0.75 2.52 Ϯ 0.29 0.83 Ϯ 0.32c 2.71 Ϯ 0.55 1.016 Ϯ 0.361d 0.950 Ϯ 0.146 (-), n ϭ 14 36.40 Ϯ 21.90 4.41 Ϯ 1.12 2.70 Ϯ 1.12 1.33 Ϯ 0.36c 2.53 Ϯ 0.75 1.435 Ϯ 0.351d 0.819 Ϯ 0.223 a (ϩ) and (-) indicate individuals with and without the ABCA1 W590L mutation, respectively. Login to comment
87 The W590L mutation site in ABCA1 resides in a highly conserved hydrophobic region within the extracellular segment of the NH2 terminus (24, 25) and is identical to amino acid 605 of ABCR. Login to comment
52 The affected individuals in the kindred were heterozygous for a G2265T substitution (Fig. 2, arrow) with predicted conversion of Trp to Leu (W590L). Login to comment
56 Pedigree of a kindred showing HDL-C segregation of W590L mutation. Login to comment
63 Significant differences between (af9;) and (afa;) individuals for the W590L mutation were noted for HDL-C (P afd; 0.009) and apoA-I (P afd; 0.036). Login to comment
76 Individuala Sex Age, years TC,b mmol/L TG, mmol/L HDL-C, mmol/L LDL-C, mmol/L apoA-I, g/L apoB, g/L I-2 (afa;) F 88 5.43 3.28 1.40 3.39 1.67 1.10 I-3 (d19;) M 81 4.63 2.20 1.06 3.13 1.21 0.95 II-1 (afa;) M 48 4.88 4.34 1.14 2.87 1.32 1.00 II-2 (afa;) F 47 5.53 3.54 1.65 3.18 2.00 1.11 II-3 (d19;) M 52 3.10 2.97 0.34 2.17 0.49 0.93 II-4 (afa;) F 54 3.95 1.63 1.65 1.96 1.54 0.60 II-5 (d19;) M 57 5.19 2.38 1.14 3.59 1.39 1.18 II-6 (afa;) F 54 3.67 1.24 1.14 2.17 1.18 0.64 II-7 (afa;) M 54 7.13 4.91 1.94 4.21 2.05 1.26 II-8 (d19;) F 40 3.80 2.45 0.88 2.43 1.06 0.86 III-1 (afa;) F 19 4.16 2.48 0.96 2.71 1.01 0.79 III-2 (afa;) M 27 3.10 2.43 1.27 1.34 1.51 0.54 III-3 (d19;) M 31 3.70 2.74 0.54 2.61 0.85 0.98 III-4 (d19;) F 28 3.80 2.35 1.03 2.30 1.29 0.80 III-5 (afa;) F 33 3.98 1.52 1.40 2.27 1.34 0.68 III-6 (afa;) F 19 3.95 2.74 0.96 2.45 1.10 0.75 III-7 (afa;) F 27 5.37 2.07 1.96 2.89 1.90 0.93 III-8 (afa;) M 10 3.64 2.25 1.01 2.20 1.15 0.77 III-9 (afa;) M 13 3.70 1.60 1.24 2.14 1.24 0.68 III-10 (afa;) F 17 3.23 3.75 0.88 1.60 1.09 0.62 Mean afe; SD (af9;), n afd; 6 41.60 afe; 12.70 4.04 afe; 0.75 2.52 afe; 0.29 0.83 afe; 0.32c 2.71 afe; 0.55 1.016 afe; 0.361d 0.950 afe; 0.146 (afa;), n afd; 14 36.40 afe; 21.90 4.41 afe; 1.12 2.70 afe; 1.12 1.33 afe; 0.36c 2.53 afe; 0.75 1.435 afe; 0.351d 0.819 afe; 0.223 a (af9;) and (afa;) indicate individuals with and without the ABCA1 W590L mutation, respectively. Login to comment