ABCA1 p.Ile178Thr
| Predicted by SNAP2: | A: N (93%), C: N (87%), D: N (93%), E: N (93%), F: N (87%), G: N (87%), H: N (93%), K: N (97%), L: N (97%), M: N (93%), N: N (97%), P: N (87%), Q: N (97%), R: N (93%), S: N (97%), T: N (93%), V: N (93%), W: D (53%), Y: N (57%), |
| Predicted by PROVEAN: | A: N, C: N, D: N, E: N, F: N, G: N, H: N, K: N, L: N, M: N, N: N, P: N, Q: N, R: N, S: N, T: N, V: N, W: N, Y: N, |
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[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.
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No. Sentence Comment
12 In addition, we studied another pedigree with a previously reported variant in LCAT [I178T] [13].
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ABCA1 p.Ile178Thr 17113061:12:85
status: NEW44 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).
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ABCA1 p.Ile178Thr 17113061:44:274
status: NEW46 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.
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ABCA1 p.Ile178Thr 17113061:46:161
status: NEW47 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.
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ABCA1 p.Ile178Thr 17113061:47:371
status: NEW