ABCMdb

PMID: 17113061

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., [PubMed]

Sentences

No. Mutations Sentence Comment

11 ABCA1 p.Asp1099Tyr ABCA1 p.Phe2009Ser ABCA1 p.Pro85Leu ABCA1 p.Arg1851Gln Materials and methods We previously identified mutations in LCAT [T321M, C-deletion (codon 168) P260X [7,8], ABCA1 [D1099Y, F2009S, P85L, R1851Q, IVS46: del T-39…-46] [9-11] and APOA1 [L159P] [12]. Login to comment 12 ABCA1 p.Ile178Thr In addition, we studied another pedigree with a previously reported variant in LCAT [I178T] [13]. Login to comment 29 ABCA1 p.Arg1851Gln ABCA1 p.Arg1851Gln All mutations were heterozygous and 3 subjects were genetic compounds (e.g., IVS46: del T-39…-46/R1851Q and 238X/T321M). Login to comment 37 ABCA1 p.Trp590Leu These data extend previous observations where increased cIMT was not associated with the ABCA1 variant, W590L [14]. Login to comment 44 ABCA1 p.Ile178Thr Based on the ARIC study [19] where the mean cIMT in 55 y-old men and women was 0.70 and 0.64 mm respectively, in association with an annual cross-sectional change of ~0.008 mm/y, 4 low HDL cases with CHD had increased cIMT (APOAI L159P, LCAT c-deletion (codon 168) and LCAT I178T), 2 had age predicted cIMT (ABCA1 mutations) and only one had a lower cIMT than predicted (LCAT P260X). Login to comment 46 ABCA1 p.Asp1099Tyr ABCA1 p.Phe2009Ser ABCA1 p.Pro85Leu ABCA1 p.Arg1851Gln ABCA1 p.Ile178Thr Therefore, while we Table 1 Genetic variants causing low HDL-C Gene Mutation Number Affected Reference LCAT c-deletion (codon 168) 2 [7] T321M 5 [7] P260X 3 [8] I178T 6 [13] ABCA1 D1099Y 5 [9] F2009S 1 [9] P85L 4 [10] R1851Q 6 [11] IVS46: del T-39…-46 6 [11] APOAI L159P 6 [12] Total 41 cases (includes 3 compound heterozygotes) Table 2 Selected demographic factors, risk factor prevalence, medication use and biochemical measurements (mean and SD) and cIMT in genetic variant HDL-C cases and controls Cases (n=41) Controls (n=73) Age (y) 44.8 (20.7) 44.8 (19.1) BMI (kg/m2 ) 28.0 (4.3) 26.4 (4.9) Hypertension (%) 10.8% 15.9% Diabetes mellitus (%) 2.7% 0% Smoking history (%) 24.3% 31.7% Antiplatelet therapy (%) 18.9% 9.7% Lipid lowering therapy (%) 21.6% 12.9% cIMT (mm) 0.66 (0.17) 0.65 (0.18) TC (mmol/l) 4.92 (1.52) 5.03 (1.06) TG (mmol/l) 2.10 (1.72) ⁎ 1.36 (0.90) HDL-C (mmol/l) 0.67 (0.36) ⁎ 1.58 (0.75) LDL-C (mmol/l) 3.28 (1.31) 2.85 (0.91) APOAI (mg/dl) 96.7 (37.9) ⁎ 151.4 (34.9) APOB (mg/dl) 123.6 (44.8) ⁎ 89.9 (26.6) ⁎ Pb0.05 cases vs. controls. Login to comment 47 ABCA1 p.Arg1851Gln ABCA1 p.Arg1851Gln ABCA1 p.Ile178Thr ABCA1 p.Ile178Thr Table 3 Gene mutations, cIMT, onset of CHD and risk factors in 7 caseswith low HDL-C Gene Mutation cIMT Age onset (y) CHD risk factors ABCA1P85L 0.64 48 Smoker, HTN, HTG ABCA1 IVS46: del T-39…-46/ 0.59 44 FCHL R1851Q APOAI L159P 0.71 41 Smoker, FCHL APOAI L159P 0.82 35 FCHL LCAT c-deletion (codon 168) 1.37 76 Smoker, HTN, HTG LCAT P260X 0.59 57 Smoker, FCHL LCAT I178T 0.69 39 FCHL Mean 0.77±0.28 60.9±18.9 Abbreviations: FCHL, familial combined hyperlipidemia; HTN, hypertension; HTG, hypertriglyceridemia. Login to comment