ABCMdb

PMID: 20581104

Jakulj L, Vissers MN, Tanck MW, Hutten BA, Stellaard F, Kastelein JJ, Dallinga-Thie GM
ABCG5/G8 polymorphisms and markers of cholesterol metabolism: systematic review and meta-analysis.
J Lipid Res. 2010 Oct;51(10):3016-23. Epub 2010 Jun 25., [PubMed]

Sentences

No. Mutations Sentence Comment

12 ABCG5 p.Gln604Glu ABCG8 p.Asp19His ABCG8 p.Thr400Lys ABCG8 p.Tyr54Cys We first investigated associations between five common ABCG5/G8 polymorphisms (p.Q604E, p.D19H, p.Y54C, p. T400K, and p.A632V) and plasma sterol levels in 245 hypercholesterolaemic individuals. Login to comment 66 ABCG5 p.Gln604Glu ABCG8 p.Asp19His ABCG8 p.Thr400Lys ABCG8 p.Tyr54Cys We genotyped five nonsynonymous polymorphisms in ABCG5/G8 [ABCG5: p.Q604E (rs6720173); ABCG8: p.D19H (rs11887534), p.Y54C (rs4148211), p.T400K (rs4148217), and p.A632V (rs6544718)] using allelic discrimination. Login to comment 67 ABCG5 p.Gln604Glu ABCG8 p.Asp19His ABCG8 p.Thr400Lys ABCG8 p.Tyr54Cys We genotyped five nonsynonymous polymorphisms in ABCG5/G8 [ABCG5: p.Q604E (rs6720173); ABCG8: p.D19H (rs11887534), p.Y54C (rs4148211), p.T400K (rs4148217), and p.A632V (rs6544718)] using allelic discrimination. Login to comment 68 ABCG5 p.Gln604Glu ABCG8 p.Asp19His ABCG8 p.Thr400Lys ABCG8 p.Tyr54Cys We genotyped five nonsynonymous polymorphisms in ABCG5/G8 [ABCG5: p.Q604E (rs6720173); ABCG8: p.D19H (rs11887534), p.Y54C (rs4148211), p.T400K (rs4148217), and p.A632V (rs6544718)] using allelic discrimination. Login to comment 90 ABCG8 p.Asp19His Analysis of the pooled data revealed that the minor allele of the p.D19H variant was associated with significantly reduced markers of cholesterol absorption and increased markers of cholesterol synthesis (Fig. 2); 83 subjects carrying the 19H allele showed decreased riers of the common variant. Login to comment 91 ABCG8 p.Asp19His Analysis of the pooled data revealed that the minor allele of the p.D19H variant was associated with significantly reduced markers of cholesterol absorption and increased markers of cholesterol synthesis (Fig. 2); 83 subjects carrying the 19H allele showed decreased riers of the common variant. Login to comment 92 ABCG8 p.Asp19His Analysis of the pooled data revealed that the minor allele of the p.D19H variant was associated with significantly reduced markers of cholesterol absorption and increased markers of cholesterol synthesis (Fig. 2); 83 subjects carrying the 19H allele showed decreased riers of the common variant. Login to comment 117 ABCG8 p.Asp19His Although these studies mostly include common variants with a minor allele frequency (MAF) greater than 0.1, two studies described a significant association between the lesser common p.D19H variant and plasma LDL-C concentrations (36, 38), although associations were relatively weak. Login to comment 118 ABCG8 p.Asp19His ABCG8 p.Asp19His We did not find any association between the p.D19H variant and baseline LDL-C levels in 155 subjects with the minor allele versus 1,842 subjects carrying the common variant (supplementary Table II). Login to comment 119 ABCG8 p.Asp19His ABCG8 p.Asp19His Although these studies mostly include common variants with a minor allele frequency (MAF) greater than 0.1, two studies described a significant association between the lesser common p.D19H variant and plasma LDL-C concentrations (36, 38), although associations were relatively weak. Login to comment 120 ABCG8 p.Asp19His We did not find any association between the p.D19H variant and baseline LDL-C levels in 155 subjects with the minor allele versus 1,842 subjects carrying the common variant (supplementary Table II). Login to comment 123 ABCG8 p.Asp19His However, in silico analysis by polyphen predicts p.D19H as a benign variant, and no relation was found between this SNP and ABCG8 mRNA expression levels in human liver tissue samples (38). Login to comment 124 ABCG8 p.Asp19His ABCG8 p.Tyr54Cys Of note, in silico analyses of the remaining four variants predicted only the p.Y54C polymorphism to be damaging. Login to comment 125 ABCG8 p.Asp19His ABCG8 p.Tyr54Cys However, in silico analysis by polyphen predicts p.D19H as a benign variant, and no relation was found between this SNP and ABCG8 mRNA expression levels in human liver tissue samples (38). Login to comment 126 ABCG8 p.Tyr54Cys Of note, in silico analyses of the remaining four variants predicted only the p.Y54C polymorphism to be damaging. Login to comment 129 ABCG8 p.Thr400Lys The p.T400K polymorphism showed similar trends with borderline significance, whereas the remaining three polymorphisms were not associated with baseline non-cholesterol sterol levels (supplementary Table II). Login to comment 130 ABCG8 p.Thr400Lys The p.T400K polymorphism showed similar trends with borderline significance, whereas the remaining three polymorphisms were not associated with baseline non-cholesterol sterol levels (supplementary Table II). Login to comment 131 ABCG8 p.Thr400Lys The p.T400K polymorphism showed similar trends with borderline significance, whereas the remaining three polymorphisms were not associated with baseline non-cholesterol sterol levels (supplementary Table II). Login to comment 132 ABCG8 p.Asp19His The p.D19H variant was associated with changes in cholesterol absorption and cholesterol synthesis markers without affecting plasma cholesterol levels. Login to comment 133 ABCG8 p.Asp19His The p.D19H variant was associated with changes in cholesterol absorption and cholesterol synthesis markers without affecting plasma cholesterol levels. Login to comment 134 ABCG8 p.Asp19His The p.D19H variant was associated with changes in cholesterol absorption and cholesterol synthesis markers without affecting plasma cholesterol levels. Login to comment 139 ABCG5 p.Gln604Glu ABCG8 p.Asp19His ABCG8 p.Thr400Lys ABCG8 p.Tyr54Cys Associations between ABCG5/G8 polymorphisms and plasma lipids and non-cholesterol sterol ratios Lipids and Lipoproteins (mmol/l) Non-Cholesterol Sterol Ratios (òe;g/mg) SNP N TC LDL-C HDL-C Triglycerides Campesterol/TC Sitosterol/TC Cholestanol/TC Lathosterol/TC Q604E QQ 171 6.16 &#b1; 0.76 4.05 &#b1; 0.61 1.54 &#b1; 0.40 1.09 [0.29-3.56] 1.45 &#b1; 0.64 1.12 &#b1; 0.53 1.49 &#b1; 0.33 1.24 &#b1; 0.49 QE/EE 72 6.23 &#b1; 0.73 4.11 &#b1; 0.63 1.49 &#b1; 0.36 1.19 [0.47-3.93] 1.47 &#b1; 0.88 1.16 &#b1; 0.63 1.46 &#b1; 0.38 1.28 &#b1; 0.57 D19H DD 219 6.19 &#b1; 0.75 4.08 &#b1; 0.61 1.52 &#b1; 0.40 1.10 [0.29-3.93] 1.49 &#b1; 0.69 1.16 &#b1; 0.55 1.49 &#b1; 0.34 1.24 &#b1; 0.49 DH/HH 24 6.04 &#b1; 0.81 3.90 &#b1; 0.63 1.60 &#b1; 0.38 1.15 [0.47-1.97] 1.24 &#b1; 0.82 0.92 &#b1; 0.53 1.38 &#b1; 0.34 1.35 &#b1; 0.64 Y54C YY 73 6.32 &#b1; 0.73 4.14 &#b1; 0.64 1.58 &#b1; 0.37 1.09 [0.45-3.93] 1.59 &#b1; 0.76 1.22 &#b1; 0.60 1.53 &#b1; 0.33 1.24 &#b1; 0.53 YC/CC 171 6.12 &#b1; 0.76 4.03 &#b1; 0.61 1.51 &#b1; 0.41 1.11 [0.29-3.56] 1.41 &#b1; 0.68 1.09 &#b1; 0.53 1.46 &#b1; 0.34 1.26 &#b1; 0.50 T400K TT 183 6.16 &#b1; 0.75 4.03 &#b1; 0.60 1.55 &#b1; 0.40 1.10 [0.29-3.93] 1.48 &#b1; 0.69 1.14 &#b1; 0.55 1.49 &#b1; 0.35 1.25 &#b1; 0.48 TK/KK 61 6.24 &#b1; 0.76 4.19 &#b1; 0.66 1.47 &#b1; 0.37 1.14 [0.47-2.61] 1.38 &#b1; 0.76 1.09 &#b1; 0.59 1.45 &#b1; 0.31 1.27 &#b1; 0.59 A632V AA 139 6.22 &#b1; 0.72 4.12 &#b1; 0.60 1.51 &#b1; 0.37 1.12 [0.33-2.90] 1.49 &#b1; 0.72 1.16 &#b1; 0.58 1.51 &#b1; 0.37 1.21 &#b1; 0.49 AV/VV 105 6.14 &#b1; 0.79 3.99 &#b1; 0.63 1.57 &#b1; 0.43 1.07 [0.29-3.93] 1.42 &#b1; 0.70 1.09 &#b1; 0.52 1.44 &#b1; 0.30 1.31 &#b1; 0.52 Values shown are means &#b1; SD. Triglycerides are shown as median [range]. Login to comment 140 ABCG5 p.Gln604Glu ABCG8 p.Asp19His ABCG8 p.Thr400Lys ABCG8 p.Tyr54Cys Associations between ABCG5/G8 polymorphisms and plasma lipids and non-cholesterol sterol ratios Lipids and Lipoproteins (mmol/l) Non-Cholesterol Sterol Ratios (òe;g/mg) SNP N TC LDL-C HDL-C Triglycerides Campesterol/TC Sitosterol/TC Cholestanol/TC Lathosterol/TC Q604E QQ 171 6.16 &#b1; 0.76 4.05 &#b1; 0.61 1.54 &#b1; 0.40 1.09 [0.29-3.56] 1.45 &#b1; 0.64 1.12 &#b1; 0.53 1.49 &#b1; 0.33 1.24 &#b1; 0.49 QE/EE 72 6.23 &#b1; 0.73 4.11 &#b1; 0.63 1.49 &#b1; 0.36 1.19 [0.47-3.93] 1.47 &#b1; 0.88 1.16 &#b1; 0.63 1.46 &#b1; 0.38 1.28 &#b1; 0.57 D19H DD 219 6.19 &#b1; 0.75 4.08 &#b1; 0.61 1.52 &#b1; 0.40 1.10 [0.29-3.93] 1.49 &#b1; 0.69 1.16 &#b1; 0.55 1.49 &#b1; 0.34 1.24 &#b1; 0.49 DH/HH 24 6.04 &#b1; 0.81 3.90 &#b1; 0.63 1.60 &#b1; 0.38 1.15 [0.47-1.97] 1.24 &#b1; 0.82 0.92 &#b1; 0.53 1.38 &#b1; 0.34 1.35 &#b1; 0.64 Y54C YY 73 6.32 &#b1; 0.73 4.14 &#b1; 0.64 1.58 &#b1; 0.37 1.09 [0.45-3.93] 1.59 &#b1; 0.76 1.22 &#b1; 0.60 1.53 &#b1; 0.33 1.24 &#b1; 0.53 YC/CC 171 6.12 &#b1; 0.76 4.03 &#b1; 0.61 1.51 &#b1; 0.41 1.11 [0.29-3.56] 1.41 &#b1; 0.68 1.09 &#b1; 0.53 1.46 &#b1; 0.34 1.26 &#b1; 0.50 T400K TT 183 6.16 &#b1; 0.75 4.03 &#b1; 0.60 1.55 &#b1; 0.40 1.10 [0.29-3.93] 1.48 &#b1; 0.69 1.14 &#b1; 0.55 1.49 &#b1; 0.35 1.25 &#b1; 0.48 TK/KK 61 6.24 &#b1; 0.76 4.19 &#b1; 0.66 1.47 &#b1; 0.37 1.14 [0.47-2.61] 1.38 &#b1; 0.76 1.09 &#b1; 0.59 1.45 &#b1; 0.31 1.27 &#b1; 0.59 A632V AA 139 6.22 &#b1; 0.72 4.12 &#b1; 0.60 1.51 &#b1; 0.37 1.12 [0.33-2.90] 1.49 &#b1; 0.72 1.16 &#b1; 0.58 1.51 &#b1; 0.37 1.21 &#b1; 0.49 AV/VV 105 6.14 &#b1; 0.79 3.99 &#b1; 0.63 1.57 &#b1; 0.43 1.07 [0.29-3.93] 1.42 &#b1; 0.70 1.09 &#b1; 0.52 1.44 &#b1; 0.30 1.31 &#b1; 0.52 Values shown are means &#b1; SD. Triglycerides are shown as median [range]. Login to comment 141 ABCG5 p.Gln604Glu ABCG8 p.Asp19His ABCG8 p.Thr400Lys ABCG8 p.Tyr54Cys Associations between ABCG5/G8 polymorphisms and plasma lipids and non-cholesterol sterol ratios Lipids and Lipoproteins (mmol/l) Non-Cholesterol Sterol Ratios (␮g/mg) SNP N TC LDL-C HDL-C Triglycerides Campesterol/TC Sitosterol/TC Cholestanol/TC Lathosterol/TC Q604E QQ 171 6.16 ± 0.76 4.05 ± 0.61 1.54 ± 0.40 1.09 [0.29-3.56] 1.45 ± 0.64 1.12 ± 0.53 1.49 ± 0.33 1.24 ± 0.49 QE/EE 72 6.23 ± 0.73 4.11 ± 0.63 1.49 ± 0.36 1.19 [0.47-3.93] 1.47 ± 0.88 1.16 ± 0.63 1.46 ± 0.38 1.28 ± 0.57 D19H DD 219 6.19 ± 0.75 4.08 ± 0.61 1.52 ± 0.40 1.10 [0.29-3.93] 1.49 ± 0.69 1.16 ± 0.55 1.49 ± 0.34 1.24 ± 0.49 DH/HH 24 6.04 ± 0.81 3.90 ± 0.63 1.60 ± 0.38 1.15 [0.47-1.97] 1.24 ± 0.82 0.92 ± 0.53 1.38 ± 0.34 1.35 ± 0.64 Y54C YY 73 6.32 ± 0.73 4.14 ± 0.64 1.58 ± 0.37 1.09 [0.45-3.93] 1.59 ± 0.76 1.22 ± 0.60 1.53 ± 0.33 1.24 ± 0.53 YC/CC 171 6.12 ± 0.76 4.03 ± 0.61 1.51 ± 0.41 1.11 [0.29-3.56] 1.41 ± 0.68 1.09 ± 0.53 1.46 ± 0.34 1.26 ± 0.50 T400K TT 183 6.16 ± 0.75 4.03 ± 0.60 1.55 ± 0.40 1.10 [0.29-3.93] 1.48 ± 0.69 1.14 ± 0.55 1.49 ± 0.35 1.25 ± 0.48 TK/KK 61 6.24 ± 0.76 4.19 ± 0.66 1.47 ± 0.37 1.14 [0.47-2.61] 1.38 ± 0.76 1.09 ± 0.59 1.45 ± 0.31 1.27 ± 0.59 A632V AA 139 6.22 ± 0.72 4.12 ± 0.60 1.51 ± 0.37 1.12 [0.33-2.90] 1.49 ± 0.72 1.16 ± 0.58 1.51 ± 0.37 1.21 ± 0.49 AV/VV 105 6.14 ± 0.79 3.99 ± 0.63 1.57 ± 0.43 1.07 [0.29-3.93] 1.42 ± 0.70 1.09 ± 0.52 1.44 ± 0.30 1.31 ± 0.52 Values shown are means ± SD. Triglycerides are shown as median [range]. Login to comment 144 ABCG5 p.Gln604Glu ABCG5 p.Gln604Glu ABCG5 p.Gln604Glu ABCG5 p.Gln604Glu ABCG5 p.Gln604Glu ABCG5 p.Gln604Glu ABCG5 p.Gln604Glu ABCG5 p.Gln604Glu ABCG5 p.Gln604Glu ABCG5 p.Gln604Glu ABCG5 p.Gln604Glu ABCG5 p.Gln604Glu ABCG5 p.Gln604Glu ABCG5 p.Gln604Glu ABCG5 p.Gln604Glu ABCG8 p.Asp19His ABCG8 p.Asp19His ABCG8 p.Asp19His ABCG8 p.Asp19His ABCG8 p.Asp19His ABCG8 p.Asp19His ABCG8 p.Asp19His ABCG8 p.Asp19His ABCG8 p.Asp19His ABCG8 p.Thr400Lys ABCG8 p.Thr400Lys ABCG8 p.Thr400Lys ABCG8 p.Thr400Lys ABCG8 p.Thr400Lys ABCG8 p.Thr400Lys ABCG8 p.Thr400Lys ABCG8 p.Thr400Lys ABCG8 p.Thr400Lys ABCG8 p.Thr400Lys ABCG8 p.Thr400Lys ABCG8 p.Thr400Lys ABCG8 p.Tyr54Cys ABCG8 p.Tyr54Cys ABCG8 p.Tyr54Cys ABCG8 p.Tyr54Cys ABCG8 p.Tyr54Cys ABCG8 p.Tyr54Cys ABCG8 p.Tyr54Cys ABCG8 p.Tyr54Cys ABCG8 p.Tyr54Cys ABCG8 p.Tyr54Cys ABCG8 p.Tyr54Cys ABCG8 p.Tyr54Cys Characteristics of studies included in the meta-analysis Reference Number of Subjects Age Male/ Female Body Mass Index Ethnicity Single Nucleotide Polymorphisms Lipids Non-Cholesterol Sterols n years n kg/m 2 Berge, 2002 (5) 148 55 &#b1; 11 74/74 Not reported Caucasian D19H, T400K, Y54C, Q604E, A632V TC CAMP, SITO, CHOLST, LATHO Weggemans, 2002 (7) 486 26.3 &#b1; 11.6 257/229 21.7 &#b1; 3.0 Caucasian Q604E TC - Gylling, 2004 (13) 262 53.1 &#b1; 8.1 143/119 26.4 &#b1; 6.5 Caucasian D19H, T400K, Y54C, Q604E, A632V TC, LDL-C, HDL-C, TG CAMP, SITO, CHOLST, LATHO Plat, 2005 (11) a 112 33 &#b1; 16 41/71 22.9 &#b1; 3.6 Caucasian T400K, Q604E, A632V LDL-C, HDL-C, TG CAMP, SITO, LATHO Acalovschi, 2006 (27) 72 e 56.3 (36-80) 30/42 30.1 &#b1; 4.9 Caucasian D19H, T400K, Y54C, Q604E, A632V TC, HDL-C, TG - Jakulj, et al. b 245 58.4 &#b1; 7.5 189/48 25.8 &#b1; 3.0 Caucasian D19H, T400K, Y54C, Q604E, A632V TC, LDL-C, HDL-C, TG CAMP, SITO, CHOLST, LATHO Miwa, 2005 (28) 100 62.4 &#b1; 12.1 48/52 23.0 &#b1; 3.5 Asian T400K, Y54C, Q604E - SITO, LATHO Wang, 2007 (29) a , c 134 54.1 &#b1; 8.1 134/0 23.2 &#b1; 2.3 Asian T400K, Y54C, Q604E TC, LDL-C, HDL-C, TG - Chen, 2008 (8) a 1046 47.0 &#b1; 9.3 894/152 24.9 &#b1; 2.4 Asian D19H, T400K, Y54C, Q604E i TC, LDL-C, HDL-C, TG - Caamano, 2008 (30) d 104 40 &#b1; 10 58/46 25.5 &#b1; 3.3 Hispanic Y54C, Q604E TC, LDL-C, HDL-C, TG - 118 44 &#b1; 7 71/47 27.6 &#b1; 4.9 Hispanic Y54C, Q604E TC, LDL-C, HDL-C, TG - Santosa, 2007 (31) a 35 49.4 &#b1; 6.7 0/35 31.4 &#b1; 2.8 Mixed f D19H, T400K, Y54C, Q604E TC, LDL-C, HDL-C, TG - Rudkowska, 2008 (32) 26 59.6 &#b1; 9.6 15/11 26.4 &#b1; 2.7 Mixed f D19H, T400K, Y54C, Q604E TC, LDL-C, HDL-C, TG - Chan, 2004 (33) a 47 54.5 &#b1; 8.4 47/0 32 &#b1; 3.6 Not reported g D19H, T400K TC, LDL-C, HDL-C, TG CAMP, SITO, LATHO Kajinami, 2004 (12) a 338 58 &#b1; 11 203/135 27.0 &#b1; 3.0 Not reported h D19H, T400K, Y54C, Q604E, A632V TC, LDL-C, HDL-C, TG - Herron, 2006 (9) a 91 31.1 &#b1; 9.2 40/51 24.8 &#b1; 4.7 Not reported h Q604E TC, LDL-C, HDL-C - Total (WM) 3364 46.7 &#b1; 10.5 2251/ 1113 23.9 &#b1; 3.5 Number and characteristics of studies included in the meta-analysis. Login to comment 145 ABCG5 p.Gln604Glu ABCG5 p.Gln604Glu ABCG5 p.Gln604Glu ABCG5 p.Gln604Glu ABCG5 p.Gln604Glu ABCG5 p.Gln604Glu ABCG5 p.Gln604Glu ABCG5 p.Gln604Glu ABCG5 p.Gln604Glu ABCG5 p.Gln604Glu ABCG5 p.Gln604Glu ABCG5 p.Gln604Glu ABCG5 p.Gln604Glu ABCG5 p.Gln604Glu ABCG5 p.Gln604Glu ABCG5 p.Gln604Glu ABCG5 p.Gln604Glu ABCG5 p.Gln604Glu ABCG5 p.Gln604Glu ABCG5 p.Gln604Glu ABCG5 p.Gln604Glu ABCG5 p.Gln604Glu ABCG5 p.Gln604Glu ABCG8 p.Asp19His ABCG8 p.Asp19His ABCG8 p.Asp19His ABCG8 p.Asp19His ABCG8 p.Asp19His ABCG8 p.Asp19His ABCG8 p.Asp19His ABCG8 p.Asp19His ABCG8 p.Asp19His ABCG8 p.Asp19His ABCG8 p.Asp19His ABCG8 p.Asp19His ABCG8 p.Asp19His ABCG8 p.Thr400Lys ABCG8 p.Thr400Lys ABCG8 p.Thr400Lys ABCG8 p.Thr400Lys ABCG8 p.Thr400Lys ABCG8 p.Thr400Lys ABCG8 p.Thr400Lys ABCG8 p.Thr400Lys ABCG8 p.Thr400Lys ABCG8 p.Thr400Lys ABCG8 p.Thr400Lys ABCG8 p.Thr400Lys ABCG8 p.Thr400Lys ABCG8 p.Thr400Lys ABCG8 p.Thr400Lys ABCG8 p.Thr400Lys ABCG8 p.Thr400Lys ABCG8 p.Thr400Lys ABCG8 p.Thr400Lys ABCG8 p.Thr400Lys ABCG8 p.Tyr54Cys ABCG8 p.Tyr54Cys ABCG8 p.Tyr54Cys ABCG8 p.Tyr54Cys ABCG8 p.Tyr54Cys ABCG8 p.Tyr54Cys ABCG8 p.Tyr54Cys ABCG8 p.Tyr54Cys ABCG8 p.Tyr54Cys ABCG8 p.Tyr54Cys ABCG8 p.Tyr54Cys ABCG8 p.Tyr54Cys ABCG8 p.Tyr54Cys ABCG8 p.Tyr54Cys ABCG8 p.Tyr54Cys ABCG8 p.Tyr54Cys ABCG8 p.Tyr54Cys ABCG8 p.Tyr54Cys ABCG8 p.Tyr54Cys ABCG8 p.Tyr54Cys ABCG8 p.Tyr54Cys ABCG8 p.Tyr54Cys TABLE3.Characteristicsofstudiesincludedinthemeta-analysis Reference Number of SubjectsAge Male/ Female BodyMass IndexEthnicitySingleNucleotidePolymorphismsLipidsNon-CholesterolSterols nyearsnkg/m 2 Berge,2002(5)14855±1174/74NotreportedCaucasianD19H,T400K,Y54C,Q604E,A632VTCCAMP,SITO,CHOLST,LATHO Weggemans,2002(7)48626.3±11.6257/22921.7±3.0CaucasianQ604ETC- Gylling,2004(13)26253.1±8.1143/11926.4±6.5CaucasianD19H,T400K,Y54C,Q604E,A632VTC,LDL-C,HDL-C,TGCAMP,SITO,CHOLST,LATHO Plat,2005(11)a 11233±1641/7122.9±3.6CaucasianT400K,Q604E,A632VLDL-C,HDL-C,TGCAMP,SITO,LATHO Acalovschi,2006(27)72 e 56.3(36-80)30/4230.1±4.9CaucasianD19H,T400K,Y54C,Q604E,A632VTC,HDL-C,TG- Jakulj,etal. b 24558.4±7.5189/4825.8±3.0CaucasianD19H,T400K,Y54C,Q604E,A632VTC,LDL-C,HDL-C,TGCAMP,SITO,CHOLST,LATHO Miwa,2005(28)10062.4±12.148/5223.0±3.5AsianT400K,Y54C,Q604E-SITO,LATHO Wang,2007(29) a,c 13454.1±8.1134/023.2±2.3AsianT400K,Y54C,Q604ETC,LDL-C,HDL-C,TG- Chen,2008(8) a 104647.0±;9.3894/15224.9±2.4AsianD19H,T400K,Y54C,Q604E i TC,LDL-C,HDL-C,TG- Caamano,2008(30) d 10440±;1058/4625.5±3.3HispanicY54C,Q604ETC,LDL-C,HDL-C,TG- 11844±771/4727.6±4.9HispanicY54C,Q604ETC,LDL-C,HDL-C,TG- Santosa,2007(31) a 3549.4±6.70/3531.4±2.8Mixed f D19H,T400K,Y54C,Q604ETC,LDL-C,HDL-C,TG- Rudkowska,2008(32)2659.6±9.615/1126.4±2.7Mixed f D19H,T400K,Y54C,Q604ETC,LDL-C,HDL-C,TG- Chan,2004(33) a 4754.5±8.447/032±3.6Notreported g D19H,T400KTC,LDL-C,HDL-C,TGCAMP,SITO,LATHO Kajinami,2004(12) a 33858±11203/13527.0±3.0Notreported h D19H,T400K,Y54C,Q604E,A632VTC,LDL-C,HDL-C,TG- Herron,2006(9) a 9131.1±9.240/5124.8±4.7Notreported h Q604ETC,LDL-C,HDL-C- Total(WM)336446.7±10.52251/111323.9±3.5 Numberandcharacteristicsofstudiesincludedinthemeta-analysis.CAMP,campesterol/TCratio;CHOLST,cholestanol/TCratio;HDL-C,HDL-cholesterol;LATHO,lathosterol/TCratio;LDL-C, LDL-cholesterol;SITO,sitosterol/TCratio;TC,totalcholesterol;TG,triglyceride;WM,weightedmean. Login to comment 155 ABCG8 p.Asp19His This GWAS did not report associations between the five missense variants of our meta-analysis and CAD risk; however, the variant associated with reduced CAD risk was a SNP in close linkage disequilibrium with the p.D19H variant. Login to comment 157 ABCG8 p.Asp19His This GWAS did not report associations between the five missense variants of our meta-analysis and CAD risk; however, the variant associated with reduced CAD risk was a SNP in close linkage disequilibrium with the p.D19H variant. Login to comment 158 ABCG8 p.Asp19His This GWAS did not report associations between the five missense variants of our meta-analysis and CAD risk; however, the variant associated with reduced CAD risk was a SNP in close linkage disequilibrium with the p.D19H variant. Login to comment 159 ABCG8 p.Asp19His ABCG8 p.Thr400Lys One study evaluated associations between p.T400K and p.D19H polymorphisms and CVD risk in a cohort of 2,012 heterozygous FH patients (22). Login to comment 160 ABCG8 p.Asp19His ABCG8 p.Thr400Lys Neither of the two variants was independently associated with total CVD risk; however, when combined p.T400K and p.D19H gene scores were calculated, a positive correlation was found. Login to comment 161 ABCG8 p.Asp19His ABCG8 p.Thr400Lys One study evaluated associations between p.T400K and p.D19H polymorphisms and CVD risk in a cohort of 2,012 heterozygous FH patients (22). Login to comment 162 ABCG8 p.Asp19His ABCG8 p.Asp19His ABCG8 p.Thr400Lys ABCG8 p.Thr400Lys Neither of the two variants was independently associated with total CVD risk; however, when combined p.T400K and p.D19H gene scores were calculated, a positive correlation was found. Login to comment 163 ABCG8 p.Asp19His ABCG8 p.Thr400Lys Neither of the two variants was independently associated with total CVD risk; however, when combined p.T400K and p.D19H gene scores were calculated, a positive correlation was found. Login to comment 166 ABCG8 p.Asp19His Associations between the ABCG8 p.D19H variant and plasma non-cholesterol sterol levels. Login to comment 168 ABCG8 p.Asp19His Associations between the ABCG8 p.D19H variant and plasma non-cholesterol sterol levels. Login to comment 169 ABCG8 p.Asp19His Associations between the ABCG8 p.D19H variant and plasma non-cholesterol sterol levels. Login to comment 281 ABCG8 p.Thr400Lys Twelve studies reported significant associations with baseline triglyceride levels, which mostly involved the p.T400K polymorphism (13, 29, 33); however, this was not consistent throughout all included studies (8, 11, 12, 27, 30-32). Login to comment 282 ABCG8 p.Thr400Lys Twelve studies reported significant associations with baseline triglyceride levels, which mostly involved the p.T400K polymorphism (13, 29, 33); however, this was not consistent throughout all included studies (8, 11, 12, 27, 30-32). Login to comment 284 ABCG8 p.Thr400Lys Twelve studies reported significant associations with baseline triglyceride levels, which mostly involved the p.T400K polymorphism (13, 29, 33); however, this was not consistent throughout all included studies (8, 11, 12, 27, 30-32). Login to comment 286 ABCG8 p.Asp19His In conclusion, this meta-analysis shows a positive association of the ABCG8 p.D19H polymorphism with decreased plasma plant sterol levels and concomitantly increased plasma lathosterol levels. Login to comment 287 ABCG8 p.Asp19His In conclusion, this meta-analysis shows a positive association of the ABCG8 p.D19H polymorphism with decreased plasma plant sterol levels and concomitantly increased plasma lathosterol levels. We did not observe any substantial associations between ABCG5/G8 polymorphisms and plasma lipid levels. Login to comment 289 ABCG8 p.Asp19His In conclusion, this meta-analysis shows a positive association of the ABCG8 p.D19H polymorphism with decreased plasma plant sterol levels and concomitantly increased plasma lathosterol levels. We did not observe any substantial associations between ABCG5/G8 polymorphisms and plasma lipid levels. Login to comment