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PMID: 15520451
Plat J, Bragt MC, Mensink RP
Common sequence variations in ABCG8 are related to plant sterol metabolism in healthy volunteers.
J Lipid Res. 2005 Jan;46(1):68-75. Epub 2004 Nov 1.,
[PubMed]
Sentences
No.
Mutations
Sentence
Comment
3
ABCG8 p.Thr400Lys
X
ABCG8 p.Thr400Lys 15520451:3:118
status:
VERIFIED
view ABCG8 p.Thr400Lys details
Cholesterol-standardized serum campesterol and sitosterol concentrations were significantly associated with the ABCG8
T400K
genotype, as were changes in serum plant sterol concentrations after consumption of plant stanols.
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43
ABCG5 p.Gln604Glu
X
ABCG5 p.Gln604Glu 15520451:43:92
status:
NEW
view ABCG5 p.Gln604Glu details
ABCG8 p.Thr400Lys
X
ABCG8 p.Thr400Lys 15520451:43:62
status:
NEW
view ABCG8 p.Thr400Lys details
These criteria resulted in the selection of three SNPs: ABCG8
T400K
, ABCG8 A632V, and ABCG5
Q604E
.
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44
ABCG5 p.Gln604Glu
X
ABCG5 p.Gln604Glu 15520451:44:92
status:
VERIFIED
view ABCG5 p.Gln604Glu details
ABCG8 p.Thr400Lys
X
ABCG8 p.Thr400Lys 15520451:44:62
status:
VERIFIED
view ABCG8 p.Thr400Lys details
These criteria resulted in the selection of three SNPs: ABCG8
T400K
, ABCG8 A632V, and ABCG5
Q604E
.
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53
ABCG5 p.Gln604Glu
X
ABCG5 p.Gln604Glu 15520451:53:242
status:
NEW
view ABCG5 p.Gln604Glu details
ABCG8 p.Thr400Lys
X
ABCG8 p.Thr400Lys 15520451:53:196
status:
NEW
view ABCG8 p.Thr400Lys details
Statistics Because of the limited number of subjects, and because plant sterol concentrations were not significantly different, heterozygous and homozygous carriers of the genetic variants [ABCG8
T400K
(TKKK), ABCG8 A632V (VVVA), and ABCG5
Q604E
(QEEE)] were combined before data analysis.
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54
ABCG5 p.Gln604Glu
X
ABCG5 p.Gln604Glu 15520451:54:242
status:
NEW
view ABCG5 p.Gln604Glu details
ABCG5 p.Gln604Glu
X
ABCG5 p.Gln604Glu 15520451:54:254
status:
VERIFIED
view ABCG5 p.Gln604Glu details
ABCG8 p.Thr400Lys
X
ABCG8 p.Thr400Lys 15520451:54:196
status:
VERIFIED
view ABCG8 p.Thr400Lys details
Statistics Because of the limited number of subjects, and because plant sterol concentrations were not significantly different, heterozygous and homozygous carriers of the genetic variants [ABCG8
T400K
(TKϩKK), ABCG8 A632V (VVϩVA)
, and
ABCG5
Q604E
(QEϩEE)] were combined before data analysis.
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60
ABCG5 p.Gln604Glu
X
ABCG5 p.Gln604Glu 15520451:60:109
status:
NEW
view ABCG5 p.Gln604Glu details
ABCG5 p.Gln604Glu
X
ABCG5 p.Gln604Glu 15520451:60:401
status:
NEW
view ABCG5 p.Gln604Glu details
ABCG8 p.Thr400Lys
X
ABCG8 p.Thr400Lys 15520451:60:62
status:
NEW
view ABCG8 p.Thr400Lys details
ABCG8 p.Thr400Lys
X
ABCG8 p.Thr400Lys 15520451:60:191
status:
NEW
view ABCG8 p.Thr400Lys details
Frequency distribution of the different genotypes in exons 8 (
T400K
) and 13 (A632V) of ABCG8 and in exon 13 (
Q604E
) of ABCG5 Subjects All Control Group Experimental Group All 112 42 70 ABCG8
T400K
TT 77 (68.7) 30 (71.4) 47 (67.1) TK 31 (27.7) 11 (26.2) 20 (28.6) KK 4 (3.6) 1 (2.4) 3 (4.3) ABCG8 A632V AA 70 (62.5) 23 (54.8) 47 (67.1) VA 37 (33.0) 17 (40.5) 20 (28.6) VV 5 (4.5) 2 (4.8) 3 (4.3) ABCG5
Q604E
QQ 81 (72.3) 33 (78.6) 48 (68.6) QE 29 (25.9) 9 (21.4) 20 (28.6) EE 2 (1.8) 0 (0) 2 (2.9) Values shown are absolute frequencies (with relative frequencies in parentheses).
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61
ABCG5 p.Gln604Glu
X
ABCG5 p.Gln604Glu 15520451:61:109
status:
VERIFIED
view ABCG5 p.Gln604Glu details
ABCG5 p.Gln604Glu
X
ABCG5 p.Gln604Glu 15520451:61:401
status:
VERIFIED
view ABCG5 p.Gln604Glu details
ABCG8 p.Thr400Lys
X
ABCG8 p.Thr400Lys 15520451:61:62
status:
VERIFIED
view ABCG8 p.Thr400Lys details
ABCG8 p.Thr400Lys
X
ABCG8 p.Thr400Lys 15520451:61:191
status:
VERIFIED
view ABCG8 p.Thr400Lys details
Frequency distribution of the different genotypes in exons 8 (
T400K
) and 13 (A632V) of ABCG8 and in exon 13 (
Q604E
) of ABCG5 Subjects All Control Group Experimental Group All 112 42 70 ABCG8
T400K
TT 77 (68.7) 30 (71.4) 47 (67.1) TK 31 (27.7) 11 (26.2) 20 (28.6) KK 4 (3.6) 1 (2.4) 3 (4.3) ABCG8 A632V AA 70 (62.5) 23 (54.8) 47 (67.1) VA 37 (33.0) 17 (40.5) 20 (28.6) VV 5 (4.5) 2 (4.8) 3 (4.3) ABCG5
Q604E
QQ 81 (72.3) 33 (78.6) 48 (68.6) QE 29 (25.9) 9 (21.4) 20 (28.6) EE 2 (1.8) 0 (0) 2 (2.9) Values shown are absolute frequencies (with relative frequencies in parentheses).
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71
ABCG5 p.Gln604Glu
X
ABCG5 p.Gln604Glu 15520451:71:109
status:
NEW
view ABCG5 p.Gln604Glu details
ABCG8 p.Thr400Lys
X
ABCG8 p.Thr400Lys 15520451:71:62
status:
NEW
view ABCG8 p.Thr400Lys details
RESULTS Frequency distributions for the genotypes in exons 8 (
T400K
) and 13 (A632V) of ABCG8 and in exon 13 (
Q604E
) of ABCG5 are shown in Table 2.
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72
ABCG5 p.Gln604Glu
X
ABCG5 p.Gln604Glu 15520451:72:109
status:
VERIFIED
view ABCG5 p.Gln604Glu details
ABCG8 p.Thr400Lys
X
ABCG8 p.Thr400Lys 15520451:72:62
status:
VERIFIED
view ABCG8 p.Thr400Lys details
RESULTS Frequency distributions for the genotypes in exons 8 (
T400K
) and 13 (A632V) of ABCG8 and in exon 13 (
Q604E
) of ABCG5 are shown in Table 2.
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79
ABCG5 p.Gln604Glu
X
ABCG5 p.Gln604Glu 15520451:79:100
status:
NEW
view ABCG5 p.Gln604Glu details
ABCG5 p.Gln604Glu
X
ABCG5 p.Gln604Glu 15520451:79:204
status:
NEW
view ABCG5 p.Gln604Glu details
ABCG5 p.Gln604Glu
X
ABCG5 p.Gln604Glu 15520451:79:243
status:
NEW
view ABCG5 p.Gln604Glu details
ABCG8 p.Thr400Lys
X
ABCG8 p.Thr400Lys 15520451:79:53
status:
NEW
view ABCG8 p.Thr400Lys details
ABCG8 p.Thr400Lys
X
ABCG8 p.Thr400Lys 15520451:79:165
status:
NEW
view ABCG8 p.Thr400Lys details
Linkage disequilibrium between genotypes in exons 8 (
T400K
) and 13 (A632V) of ABCG8 and in exon 13 (
Q604E
) of ABCG5 Locus 1 Locus 2 D 95% Confidence Interval ABCG8
T400K
ABCG8 A632V 0.29 0.03-0.76 ABCG5
Q604E
0.81 0.06-0.97 ABCG8 A632V ABCG5
Q604E
0.0 0.01-0.22 D and the corresponding 95% confidence intervals were calculated by using all 112 subjects included in the study.
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80
ABCG5 p.Gln604Glu
X
ABCG5 p.Gln604Glu 15520451:80:100
status:
VERIFIED
view ABCG5 p.Gln604Glu details
ABCG5 p.Gln604Glu
X
ABCG5 p.Gln604Glu 15520451:80:204
status:
NEW
view ABCG5 p.Gln604Glu details
ABCG5 p.Gln604Glu
X
ABCG5 p.Gln604Glu 15520451:80:210
status:
VERIFIED
view ABCG5 p.Gln604Glu details
ABCG5 p.Gln604Glu
X
ABCG5 p.Gln604Glu 15520451:80:243
status:
NEW
view ABCG5 p.Gln604Glu details
ABCG5 p.Gln604Glu
X
ABCG5 p.Gln604Glu 15520451:80:249
status:
VERIFIED
view ABCG5 p.Gln604Glu details
ABCG5 p.Gln604Glu
X
ABCG5 p.Gln604Glu 15520451:80:643
status:
NEW
view ABCG5 p.Gln604Glu details
ABCG5 p.Gln604Glu
X
ABCG5 p.Gln604Glu 15520451:80:1292
status:
NEW
view ABCG5 p.Gln604Glu details
ABCG8 p.Thr400Lys
X
ABCG8 p.Thr400Lys 15520451:80:53
status:
VERIFIED
view ABCG8 p.Thr400Lys details
ABCG8 p.Thr400Lys
X
ABCG8 p.Thr400Lys 15520451:80:165
status:
NEW
view ABCG8 p.Thr400Lys details
ABCG8 p.Thr400Lys
X
ABCG8 p.Thr400Lys 15520451:80:171
status:
VERIFIED
view ABCG8 p.Thr400Lys details
ABCG8 p.Thr400Lys
X
ABCG8 p.Thr400Lys 15520451:80:319
status:
NEW
view ABCG8 p.Thr400Lys details
ABCG8 p.Thr400Lys
X
ABCG8 p.Thr400Lys 15520451:80:936
status:
NEW
view ABCG8 p.Thr400Lys details
Linkage disequilibrium between genotypes in exons 8 (
T400K
) and 13 (A632V) of ABCG8 and in exon 13 (
Q604E
) of ABCG5 Locus 1 Locus 2 DЈ 95% Confidence Interval
ABCG8
T400K
ABCG8 A632V 0.29 0.03-0.76
ABCG5
Q604E
0.81 0.06-0.97 ABCG8 A632V
ABCG5
Q604E
0.0 -0.01-0.22 DЈ and the corresponding 95% confidence int
erval
s were calculated by using all 112 subjects included in the study.
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81
ABCG5 p.Gln604Glu
X
ABCG5 p.Gln604Glu 15520451:81:643
status:
NEW
view ABCG5 p.Gln604Glu details
ABCG5 p.Gln604Glu
X
ABCG5 p.Gln604Glu 15520451:81:812
status:
VERIFIED
view ABCG5 p.Gln604Glu details
ABCG5 p.Gln604Glu
X
ABCG5 p.Gln604Glu 15520451:81:1292
status:
NEW
view ABCG5 p.Gln604Glu details
ABCG5 p.Gln604Glu
X
ABCG5 p.Gln604Glu 15520451:81:1696
status:
VERIFIED
view ABCG5 p.Gln604Glu details
ABCG8 p.Thr400Lys
X
ABCG8 p.Thr400Lys 15520451:81:0
status:
NEW
view ABCG8 p.Thr400Lys details
ABCG8 p.Thr400Lys
X
ABCG8 p.Thr400Lys 15520451:81:319
status:
NEW
view ABCG8 p.Thr400Lys details
ABCG8 p.Thr400Lys
X
ABCG8 p.Thr400Lys 15520451:81:356
status:
VERIFIED
view ABCG8 p.Thr400Lys details
ABCG8 p.Thr400Lys
X
ABCG8 p.Thr400Lys 15520451:81:936
status:
NEW
view ABCG8 p.Thr400Lys details
ABCG8 p.Thr400Lys
X
ABCG8 p.Thr400Lys 15520451:81:1208
status:
VERIFIED
view ABCG8 p.Thr400Lys details
TABLE
4. Relationships between genetic polymorphisms in ABCG8 and ABCG5 with absolute and cholesterol-standardized serum noncholesterol sterol concentrations Subjects Campesterol Sitosterol Lathosterol Campestanol Sitostanol Absolute concentrations (mol/l) All 15.8 Ϯ 5.3 6.0 Ϯ 2.4 5.2 Ϯ 2.1 0
.5 &#
x3ee; 0.3 0.4 Ϯ 0.2 ABCG8
T400K
TT 16.9 Ϯ 5.5 6.6 Ϯ 2.6 5.0 Ϯ 2.1 0.5 Ϯ 0.4 0.4 Ϯ 0.2 TK/KK 13.5 Ϯ 3.8 4.8 Ϯ 1.4 5.7 Ϯ 2.1 0.5 Ϯ 0.3 0.4 Ϯ 0.2 P value Ͻ0.001 Ͻ0.001 0.070 0.887 0.675 ABCG8 A632V AA 16.3 Ϯ 5.6 6.2 Ϯ 2.6 5.1 Ϯ
; 2.0
0.5 Ϯ 0.3 0.4 Ϯ 0.2 VV/VA 15.1 Ϯ 4.8 5.7 Ϯ 2.1 5.4 Ϯ 2.4 0.6 Ϯ 0.4 0.4 Ϯ 0.2 P value 0.280 0.266 0.516 0.349 0.759 ABCG5
Q604E
QQ 16.3 Ϯ 5.4 6.3 Ϯ 2.5 5.1 Ϯ 2.1 0.5 Ϯ 0.3 0.4 Ϯ 0.2 QE/EE 14.6 Ϯ 5.0 5.4 Ϯ
2.2
5.4 Ϯ 2.3 0.6 Ϯ 0.4 0.4 Ϯ 0.2 P value 0.125 0.093 0.517 0.043 0.768 Cholesterol-standardized concentrations (102 ϫ mol/mmol cholesterol) All 303.4 Ϯ 98.0 115.0 Ϯ 44.5 97.3 Ϯ 33.5 9.8 Ϯ 6.6 7.6 Ϯ 4.3 ABCG8
T400K
TT 324.2 Ϯ 98.5 125.2 Ϯ 45.8 93.2 Ϯ 35.0 9.6 Ϯ 6.8 7.5
ee; 4.4 TK/KK 257.7 Ϯ 80.8 92.4 Ϯ 31.9 106.4 Ϯ 28.4 10.2 Ϯ 6.1 7.7 Ϯ 3.9 P value Ͻ0.001 Ͻ0.001 0.053 0.636 0.862 ABCG8 A632V AA 305.8 Ϯ 95.3 117.3 Ϯ 47.3 95.2 Ϯ 32.2 9.3 Ϯ 6.1 7.6 Ϯ 4.2 VV/VA 299.3 Ϯ 103.3 111.0 Ϯ 39.8 101.0 Ϯ 35.8 10.6 Ϯ 7.2 7.6 Ϯ 4.4 P value 0.736 0.467 0.377 0.332 0.938 ABCG5
Q604E
QQ 310.5 Ϯ 98.8 118.3 Ϯ 43.7 95.3 Ϯ 34.8 8.9 Ϯ 5.7 7.6 Ϯ 4.3 QE/EE 284.8 Ϯ 94.9 106.2 Ϯ 46.2 102.7 Ϯ 29.9 11.9 Ϯ 8.1 7.6 Ϯ 4.2 P value 0.216 0.198 0.298 0.029 0.987 Values shown are means Ϯ SD and were analyzed after a 4-week period of consumption of rapeseed oil-based margarine and shortening.
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82
ABCG8 p.Thr400Lys
X
ABCG8 p.Thr400Lys 15520451:82:0
status:
VERIFIED
view ABCG8 p.Thr400Lys details
T400K
genotype (Table 4).
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86
ABCG5 p.Gln604Glu
X
ABCG5 p.Gln604Glu 15520451:86:37
status:
NEW
view ABCG5 p.Gln604Glu details
Subjects with the QQ genotype (ABCG5
Q604E
) showed significantly higher serum LDL cholesterol concentrations compared with QE/EE subjects (Table 5).
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87
ABCG5 p.Gln604Glu
X
ABCG5 p.Gln604Glu 15520451:87:37
status:
VERIFIED
view ABCG5 p.Gln604Glu details
Subjects with the QQ genotype (ABCG5
Q604E
) showed significantly higher serum LDL cholesterol concentrations compared with QE/EE subjects (Table 5).
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91
ABCG8 p.Thr400Lys
X
ABCG8 p.Thr400Lys 15520451:91:129
status:
NEW
view ABCG8 p.Thr400Lys details
Changes in cholesterol-standardized serum campesterol and sitosterol concentrations were significantly associated with the ABCG8
T400K
polymorphism (Table 6, Fig. 1).
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92
ABCG8 p.Thr400Lys
X
ABCG8 p.Thr400Lys 15520451:92:129
status:
VERIFIED
view ABCG8 p.Thr400Lys details
Changes in cholesterol-standardized serum campesterol and sitosterol concentrations were significantly associated with the ABCG8
T400K
polymorphism (Table 6, Fig. 1).
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94
ABCG8 p.Thr400Lys
X
ABCG8 p.Thr400Lys 15520451:94:105
status:
NEW
view ABCG8 p.Thr400Lys details
Additional analysis to evaluate the association between the three different genotype groups of the ABCG8
T400K
polymorphism (TT, TK, and KK) with changes in serum plant sterol and lipoprotein concentrations suggested an allele-dependent relation for both cholesterol-standardized serum campesterol and sitosterol concentrations (Fig. 1).
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95
ABCG8 p.Thr400Lys
X
ABCG8 p.Thr400Lys 15520451:95:105
status:
VERIFIED
view ABCG8 p.Thr400Lys details
Additional analysis to evaluate the association between the three different genotype groups of the ABCG8
T400K
polymorphism (TT, TK, and KK) with changes in serum plant sterol and lipoprotein concentrations suggested an allele-dependent relation for both cholesterol-standardized serum campesterol and sitosterol concentrations (Fig. 1).
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96
ABCG8 p.Thr400Lys
X
ABCG8 p.Thr400Lys 15520451:96:253
status:
NEW
view ABCG8 p.Thr400Lys details
Cholesterol-standardized campesterol (A), sitosterol (B), and LDL cholesterol (C) concentrations at the end of the run-in period (upper panels) and the change during the stanol ester feeding period (lower panels) in the different genotypes of the ABCG8
T400K
polymorphism.
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97
ABCG8 p.Thr400Lys
X
ABCG8 p.Thr400Lys 15520451:97:253
status:
VERIFIED
view ABCG8 p.Thr400Lys details
Cholesterol-standardized campesterol (A), sitosterol (B), and LDL cholesterol (C) concentrations at the end of the run-in period (upper panels) and the change during the stanol ester feeding period (lower panels) in the different genotypes of the ABCG8
T400K
polymorphism.
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100
ABCG5 p.Gln604Glu
X
ABCG5 p.Gln604Glu 15520451:100:468
status:
NEW
view ABCG5 p.Gln604Glu details
ABCG8 p.Thr400Lys
X
ABCG8 p.Thr400Lys 15520451:100:230
status:
NEW
view ABCG8 p.Thr400Lys details
TABLE 5. Relationships between genetic polymorphisms in ABCG8 and ABCG5 with serum lipid and lipoprotein concentrations Subjects LDL Cholesterol HDL Cholesterol Triacylglycerol mmol/l All 2.95 0.78 1.59 0.38 0.92 0.52 ABCG8
T400K
TT 2.97 0.74 1.59 0.37 0.85 0.47 TK/KK 2.89 0.86 1.60 0.40 1.08 0.58 P value 0.622 0.976 0.025 ABCG8 A632V AA 3.03 0.78 1.58 0.39 0.91 0.48 VV/VA 2.81 0.77 1.61 0.36 0.93 0.58 P value 0.137 0.666 0.883 ABCG5
Q604E
QQ 3.04 0.75 1.56 0.35 0.89 0.45 QE/EE 2.70 0.81 1.68 0.43 0.99 0.65 P value 0.039 0.145 0.342 Values shown are means SD and were analyzed after a 4-week period of consumption of rapeseed oil-based margarine and shortening.
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101
ABCG5 p.Gln604Glu
X
ABCG5 p.Gln604Glu 15520451:101:468
status:
NEW
view ABCG5 p.Gln604Glu details
ABCG5 p.Gln604Glu
X
ABCG5 p.Gln604Glu 15520451:101:558
status:
VERIFIED
view ABCG5 p.Gln604Glu details
ABCG8 p.Thr400Lys
X
ABCG8 p.Thr400Lys 15520451:101:230
status:
NEW
view ABCG8 p.Thr400Lys details
ABCG8 p.Thr400Lys
X
ABCG8 p.Thr400Lys 15520451:101:248
status:
VERIFIED
view ABCG8 p.Thr400Lys details
TABLE 5. Relationships between genetic polymorphisms in ABCG8 and ABCG5 with serum lipid and lipoprotein concentrations Subjects LDL Cholesterol HDL Cholesterol Triacylglycerol mmol/l All 2.95 Ϯ 0.78 1.59 Ϯ 0.38 0.92 &
#x3ee
; 0.52 ABCG8
T400K
TT 2.97 Ϯ 0.74 1.59 Ϯ 0.37 0.85 Ϯ 0.47 TK/KK 2.89 Ϯ 0.86 1.60 Ϯ 0.40 1.08 Ϯ 0.58 P value 0.622 0.976 0.025 ABCG8 A632V AA 3.03 Ϯ 0.78 1.58 Ϯ 0.39 0.91 Ϯ 0.48 VV
/VA 2
.81 Ϯ 0.77 1.61 Ϯ 0.36 0.93 Ϯ 0.58 P value 0.137 0.666 0.883 ABCG5
Q604E
QQ 3.04 Ϯ 0.75 1.56 Ϯ 0.35 0.89 Ϯ 0.45 QE/EE 2.70 Ϯ 0.81 1.68 Ϯ 0.43 0.99 Ϯ 0.65 P value 0.039 0.145 0.342 Values shown are means Ϯ SD and were analyzed after a 4-week period of consumption of rapeseed oil-based margarine and shortening.
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102
ABCG8 p.Thr400Lys
X
ABCG8 p.Thr400Lys 15520451:102:99
status:
NEW
view ABCG8 p.Thr400Lys details
Changes in serum campesterol concentrations showed a comparable association pattern with the ABCG8
T400K
genotype.
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103
ABCG8 p.Thr400Lys
X
ABCG8 p.Thr400Lys 15520451:103:99
status:
VERIFIED
view ABCG8 p.Thr400Lys details
Changes in serum campesterol concentrations showed a comparable association pattern with the ABCG8
T400K
genotype.
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113
ABCG5 p.Gln604Glu
X
ABCG5 p.Gln604Glu 15520451:113:1012
status:
NEW
view ABCG5 p.Gln604Glu details
ABCG5 p.Gln604Glu
X
ABCG5 p.Gln604Glu 15520451:113:1804
status:
NEW
view ABCG5 p.Gln604Glu details
ABCG8 p.Thr400Lys
X
ABCG8 p.Thr400Lys 15520451:113:686
status:
NEW
view ABCG8 p.Thr400Lys details
ABCG8 p.Thr400Lys
X
ABCG8 p.Thr400Lys 15520451:113:1452
status:
NEW
view ABCG8 p.Thr400Lys details
However, if ABCG8 transports the same proportion of plant sterols out of the enterocytes and hepatocytes into the lumen and bile, respectively, as before plant stanol ester TABLE 6. Relationships between genetic polymorphisms in ABCG8 and ABCG5 with changes in absolute and cholesterol-standardized serum noncholesterol sterol concentrations after consumption of plant stanol esters Subjects Campesterol Sitosterol Lathosterol Campestanol Sitostanol Absolute concentrations (mol/l) Experimental group Control 0.5 2.2 0.5 1.2 0.0 1.1 0.0 0.4 0.0 0.2 Stanol 6.3 3.9 3.0 2.1 0.2 1.4 0.3 0.4 0.3 0.2 P value 0.001 0.001 0.001 0.001 0.001 Genotype group ABCG8
T400K
TT 7.0 4.4 3.4 2.3 0.2 1.2 0.2 0.4 0.3 0.2 TK/KK 4.9 2.4 2.1 0.9 0.2 1.7 0.3 0.4 0.3 0.2 P value 0.042 0.017 0.989 0.526 0.967 ABCG8 A632V AA 6.5 4.5 2.9 2.3 0.3 1.1 0.3 0.4 0.3 0.2 VV/VA 6.0 2.7 3.0 1.6 0.2 1.3 0.2 0.4 0.3 0.2 P value 0.598 0.831 0.836 0.832 0.395 ABCG5
Q604E
QQ 6.6 4.3 3.1 2.3 0.1 1.5 0.2 0.4 0.3 0.2 QE/EE 5.8 3.1 2.7 1.6 0.6 1.2 0.2 0.4 0.4 0.2 P value 0.448 0.413 0.185 0.956 0.097 Cholesterol-standardized concentrations (102 mol/mmol cholesterol) Experimental group Control 5.9 39.2 7.8 22.4 0.5 19.5 0.6 7.2 0.4 4.0 Stanol 103.1 70.6 49.3 34.9 17.4 22.2 6.3 8.1 8.2 4.5 P value 0.001 0.001 0.001 0.001 0.001 Genotype group ABCG8
T400K
TT 116.7 76.5 57.1 38.3 16.5 19.8 6.1 8.3 8.4 4.5 TK/KK 75.4 46.9 33.5 19.0 19.2 26.7 6.8 7.6 7.7 4.6 P value 0.020 0.007 0.624 0.737 0.541 ABCG8 A632V AA 107.3 75.4 49.3 38.8 16.0 23.9 6.1 8.3 8.3 4.4 VV/VA 94.6 60.3 49.4 25.9 20.2 18.3 6.7 7.8 8.0 4.9 P value 0.483 0.998 0.465 0.756 0.780 ABCG5
Q604E
QQ 106.3 75.6 50.9 36.9 14.7 21.3 6.3 8.2 7.6 4.2 QE/EE 96.1 59.2 46.0 30.6 23.2 23.5 6.3 7.9 9.5 4.9 P value 0.579 0.596 0.140 0.997 0.087 Values shown are means SD. Changes in all parameters were calculated as the difference between values at the end of the run-in period (weeks 3 and 4) and the experimental period (weeks 11 and 12).
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114
ABCG5 p.Gln604Glu
X
ABCG5 p.Gln604Glu 15520451:114:1012
status:
NEW
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ABCG5 p.Gln604Glu
X
ABCG5 p.Gln604Glu 15520451:114:1229
status:
VERIFIED
view ABCG5 p.Gln604Glu details
ABCG5 p.Gln604Glu
X
ABCG5 p.Gln604Glu 15520451:114:1804
status:
NEW
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ABCG5 p.Gln604Glu
X
ABCG5 p.Gln604Glu 15520451:114:2304
status:
VERIFIED
view ABCG5 p.Gln604Glu details
ABCG8 p.Thr400Lys
X
ABCG8 p.Thr400Lys 15520451:114:686
status:
NEW
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ABCG8 p.Thr400Lys
X
ABCG8 p.Thr400Lys 15520451:114:783
status:
VERIFIED
view ABCG8 p.Thr400Lys details
ABCG8 p.Thr400Lys
X
ABCG8 p.Thr400Lys 15520451:114:1452
status:
NEW
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ABCG8 p.Thr400Lys
X
ABCG8 p.Thr400Lys 15520451:114:1832
status:
VERIFIED
view ABCG8 p.Thr400Lys details
However, if ABCG8 transports the same proportion of plant sterols out of the enterocytes and hepatocytes into the lumen and bile, respectively, as before plant stanol ester TABLE 6. Relationships between genetic polymorphisms in ABCG8 and ABCG5 with changes in absolute and cholesterol-standardized serum noncholesterol sterol concentrations after consumption of plant stanol esters Subjects Campesterol Sitosterol Lathosterol Campestanol Sitostanol Absolute concentrations (mol/l) Experimental group Control -0.5 Ϯ 2.2 -0.5 Ϯ 1.2 0.0 Ϯ 1.1 -0.0 Ϯ 0.4 0.0 Ϯ 0.2 Stanol -6.3 Ϯ 3.9 -3.0 Ϯ 2.1 0.2 Ϯ 1.4 0.3 Ϯ 0.4 0.3 Ϯ 0
.2 P
value Ͻ0.001 Ͻ0.001 Ͻ0.001 Ͻ0.001 Ͻ0.001 Genotype group ABCG8
T400K
TT -7.0 Ϯ 4.4 -3.4 Ϯ 2.3 0.2 Ϯ 1.2 0.2 Ϯ 0.4 0.3 Ϯ 0.2 TK/KK -4.9 Ϯ 2.4 -2.1 Ϯ 0.9 0.2 Ϯ 1.7 0.3 Ϯ 0.4 0.3 Ϯ 0.2 P value 0.042 0.017 0.989 0.526 0.967 ABCG8 A632V
AA -6
.5 Ϯ 4.5 -2.9 Ϯ 2.3 0.3 Ϯ 1.1 0.3 Ϯ 0.4 0.3 Ϯ 0.2 VV/VA -6.0 Ϯ 2.7 -3.0 Ϯ 1.6 0.2 Ϯ 1.3 0.2 Ϯ 0.4 0.3 Ϯ 0.2 P value 0.598 0.831 0.836 0.832 0.395 ABCG5
Q604E
QQ -6.6 Ϯ 4.3 -3.1 Ϯ 2.3 0.1 Ϯ 1.5 0.2 Ϯ 0.4 0.3 Ϯ 0.2 QE/EE -5.8 Ϯ 3.1 -2.7 Ϯ 1.6 0.6 Ϯ 1.2 0.2 Ϯ 0.4 0.4 Ϯ 0.2 P value 0.448 0.413 0.185 0.956 0.097 Choles
terol
-standardized concentrations (102 ϫ mol/mmol cholesterol) Experimental group Control -5.9 Ϯ 39.2 -7.8 Ϯ 22.4 0.5 Ϯ 19.5 -0.6 Ϯ 7.2 0.4 Ϯ 4.0 Stanol -103.1 Ϯ 70.6 -49.3 Ϯ 34.9 17.4 Ϯ 22.2 6.3 Ϯ 8.1 8.2 Ϯ 4.5 P value Ͻ0.001 Ͻ0.001 Ͻ0.001 Ͻ0.001 Ͻ
;0.00
1 Genotype group ABCG8
T400K
TT -116.7 Ϯ 76.5 -57.1 Ϯ 38.3 16.5 Ϯ 19.8 6.1 Ϯ 8.3 8.4 Ϯ 4.5 TK/KK -75.4 Ϯ 46.9 -33.5 Ϯ 19.0 19.2 Ϯ 26.7 6.8 Ϯ 7.6 7.7 Ϯ 4.6 P value 0.020 0.007 0.624 0.737 0.541 ABCG8 A632V AA -107.3 Ϯ 75.4 -49.3 Ϯ 38.8 16.0 Ϯ 23.9 6.1 Ϯ 8.3 8.3 Ϯ 4.4 VV/VA -94.6 Ϯ 60.3 -49.4 Ϯ 25.9 20.2 Ϯ 18.3 6.7 Ϯ 7.8 8.0 Ϯ 4.9 P value 0.483 0.998 0.465 0.756 0.780 ABCG5
Q604E
QQ -106.3 Ϯ 75.6 -50.9 Ϯ 36.9 14.7 Ϯ 21.3 6.3 Ϯ 8.2 7.6 Ϯ 4.2 QE/EE -96.1 Ϯ 59.2 -46.0 Ϯ 30.6 23.2 Ϯ 23.5 6.3 Ϯ 7.9 9.5 Ϯ 4.9 P value 0.579 0.596 0.140 0.997 0.087 Values shown are means Ϯ SD. Changes in all parameters were calculated as the difference between values at the end of the run-in period (weeks 3 and 4) and the experimental period (weeks 11 and 12).
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115
ABCG8 p.Thr400Lys
X
ABCG8 p.Thr400Lys 15520451:115:75
status:
NEW
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More detailed studies on the effects of the functional consequences of the
T400K
polymorphism on plant sterol metabolism are needed, which can be obtained through the development of specifically designed cell or transgenic animal models carrying this genetic variation.
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116
ABCG8 p.Thr400Lys
X
ABCG8 p.Thr400Lys 15520451:116:75
status:
VERIFIED
view ABCG8 p.Thr400Lys details
ABCG8 p.Thr400Lys
X
ABCG8 p.Thr400Lys 15520451:116:128
status:
NEW
view ABCG8 p.Thr400Lys details
More detailed studies on the effects of the functional consequences of the
T400K
polymorphism on plant sterol metabolism are nee
ded,
which can be obtained through the development of specifically designed cell or transgenic animal models carrying this genetic variation.
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117
ABCG8 p.Thr400Lys
X
ABCG8 p.Thr400Lys 15520451:117:128
status:
VERIFIED
view ABCG8 p.Thr400Lys details
Concerning the potential functionality of the different genotypes, it should be remarked that the polymorphic site of the ABCG8
T400K
polymorphisms is located in a coding region but is predicted not to contain a transmembrane domain, a signature, or a Walker motif (15).
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131
ABCG5 p.Gln604Glu
X
ABCG5 p.Gln604Glu 15520451:131:57
status:
NEW
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Weggemans et al. (30) found that subjects with the ABCG5
Q604E
EE genotype had higher serum cholesterol concentrations than carriers with the Q allele.
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132
ABCG5 p.Gln604Glu
X
ABCG5 p.Gln604Glu 15520451:132:57
status:
VERIFIED
view ABCG5 p.Gln604Glu details
Weggemans et al. (30) found that subjects with the ABCG5
Q604E
EE genotype had higher serum cholesterol concentrations than carriers with the Q allele.
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134
ABCG8 p.Asp19His
X
ABCG8 p.Asp19His 15520451:134:90
status:
NEW
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In a recent study, a statistically significant association was observed between the ABCG8
D19H
polymorphism and the proportional reduction in LDL cholesterol during atorvastatin treatment (31).
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135
ABCG8 p.Asp19His
X
ABCG8 p.Asp19His 15520451:135:90
status:
VERIFIED
view ABCG8 p.Asp19His details
In a recent study, a statistically significant association was observed between the ABCG8
D19H
polymorphism and the proportional reduction in LDL cholesterol during atorvastatin treatment (31).
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138
ABCG8 p.Thr400Lys
X
ABCG8 p.Thr400Lys 15520451:138:38
status:
NEW
view ABCG8 p.Thr400Lys details
Furthermore, the observation that the
T400K
polymorphism in ABCG8 is associated with changes in plant sterol levels with stanol ester treatment, but not with changes in the cholesterol levels, suggests that individual variation in the cholesterol-lowering efficacy of plant stanols is not strongly determined by the magnitude of the reduction in intestinal cholesterol absorption achieved.
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139
ABCG8 p.Thr400Lys
X
ABCG8 p.Thr400Lys 15520451:139:38
status:
VERIFIED
view ABCG8 p.Thr400Lys details
Furthermore, the observation that the
T400K
polymorphism in ABCG8 is associated with changes in plant sterol levels with stanol ester treatment, but not with changes in the cholesterol levels, suggests that individual variation in the cholesterol-lowering efficacy of plant stanols is not strongly determined by the magnitude of the reduction in intestinal cholesterol absorption achieved.
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141
ABCG5 p.Gln604Glu
X
ABCG5 p.Gln604Glu 15520451:141:595
status:
NEW
view ABCG5 p.Gln604Glu details
ABCG8 p.Thr400Lys
X
ABCG8 p.Thr400Lys 15520451:141:347
status:
NEW
view ABCG8 p.Thr400Lys details
TABLE 7. Relationships between genetic polymorphisms in ABCG8 and ABCG5 with changes in lipid and lipoprotein concentrations after consumption of plant stanol esters Subjects LDL Cholesterol HDL Cholesterol Triacylglycerol Control 0.06 0.36 0.01 0.16 0.02 0.23 Stanols 0.42 0.31 0.01 0.12 0.04 0.30 P value 0.001 0.903 0.272 ABCG8
T400K
TT 0.43 0.32 0.02 0.11 0.01 0.22 TK/KK 0.38 0.30 0.01 0.13 0.09 0.42 P value 0.531 0.345 0.304 ABCG8 A632V AA 0.42 0.32 0.01 0.12 0.00 0.25 VV/VA 0.41 0.29 0.00 0.13 0.10 0.38 P value 0.935 0.588 0.199 ABCG5
Q604E
QQ 0.44 0.30 0.01 0.10 0.01 0.34 QE/EE 0.36 0.34 0.01 0.16 0.09 0.18 P value 0.297 0.368 0.357 Values shown are means SD. Changes in all parameters were calculated as the difference between values at the end of the run-in period (weeks 3 and 4) and the experimental period (weeks 11 and 12).
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142
ABCG5 p.Gln604Glu
X
ABCG5 p.Gln604Glu 15520451:142:595
status:
NEW
view ABCG5 p.Gln604Glu details
ABCG5 p.Gln604Glu
X
ABCG5 p.Gln604Glu 15520451:142:709
status:
VERIFIED
view ABCG5 p.Gln604Glu details
ABCG8 p.Thr400Lys
X
ABCG8 p.Thr400Lys 15520451:142:347
status:
NEW
view ABCG8 p.Thr400Lys details
ABCG8 p.Thr400Lys
X
ABCG8 p.Thr400Lys 15520451:142:389
status:
VERIFIED
view ABCG8 p.Thr400Lys details
TABLE 7. Relationships between genetic polymorphisms in ABCG8 and ABCG5 with changes in lipid and lipoprotein concentrations after consumption of plant stanol esters Subjects LDL Cholesterol HDL Cholesterol Triacylglycerol Control -0.06 Ϯ 0.36 0.01 Ϯ 0.16 0.02 Ϯ 0.23 Stanols -0.42 Ϯ 0.31 0.01 Ϯ 0.12 -0.04 Ϯ 0.
30 P
value Ͻ0.001 0.903 0.272 ABCG8
T400K
TT -0.43 Ϯ 0.32 0.02 Ϯ 0.11 -0.01 Ϯ 0.22 TK/KK -0.38 Ϯ 0.30 -0.01 Ϯ 0.13 -0.09 Ϯ 0.42 P value 0.531 0.345 0.304 ABCG8 A632V AA -0.42 Ϯ 0.32 0.01 Ϯ 0.12
-0.00
Ϯ 0.25 VV/VA -0.41 Ϯ 0.29 -0.00 Ϯ 0.13 -0.10 Ϯ 0.38 P value 0.935 0.588 0.199 ABCG5
Q604E
QQ -0.44 Ϯ 0.30 0.01 Ϯ 0.10 -0.01 Ϯ 0.34 QE/EE -0.36 Ϯ 0.34 -0.01 Ϯ 0.16 -0.09 Ϯ 0.18 P value 0.297 0.368 0.357 Values shown are means Ϯ SD. Changes in all parameters were calculated as the difference between values at the end of the run-in period (weeks 3 and 4) and the experimental period (weeks 11 and 12).
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