ABCMdb

PMID: 17612515

Wang Y, Jiang ZY, Fei J, Xin L, Cai Q, Jiang ZH, Zhu ZG, Han TQ, Zhang SD
ATP binding cassette G8 T400K polymorphism may affect the risk of gallstone disease among Chinese males.
Clin Chim Acta. 2007 Sep;384(1-2):80-5. Epub 2007 Jun 16., [PubMed]

Sentences

No. Mutations Sentence Comment

2 ABCG5 p.Gln604Glu ABCG8 p.Asp19His ABCG8 p.Thr400Lys ABCG8 p.Tyr54Cys To investigate a possible association between transporter gene polymorphism and gallstone formation, we examined five common polymorphisms in the ABCG5 (Q604E) and ABCG8 (D19H, Y54C, T400K, A632V) genes in patients with gallstone disease (GS). Login to comment 6 ABCG8 p.Thr400Lys ABCG8 p.Tyr54Cys Results: 2 SNPs of ABCG8 gene (Y54C and T400K) showed strong linkage disequilibrium (D'=0.824, r2 =0.579). Login to comment 7 ABCG8 p.Thr400Lys Male carriers of the less frequent K allele of ABCG8 T400K had a 2.31-fold elevated risk [95% confidence interval (CI) 1.12~4.76, P=0.023] for gallstone disease compared to male with the common genotype after the adjustment for age, body mass index. Login to comment 10 ABCG8 p.Thr400Lys Conclusions: These findings indicate that the T400K polymorphism in ABCG8 may be associated with the incidence of gallstone disease in males. Login to comment 24 ABCG5 p.Gln604Glu ABCG5 p.Gln604Glu ABCG8 p.Asp19His ABCG8 p.Asp19His ABCG8 p.Thr400Lys ABCG8 p.Thr400Lys ABCG8 p.Tyr54Cys ABCG8 p.Tyr54Cys Of these variants, it is suggested that 5 non-synonymous single nucleotide polymorphisms (SNPs) in the ABCG5 (Q604E) and ABCG8 (D19H, Y54C, T400K, A632V) coding sequences may effect plasma plant sterol or cholesterol levels [11-14]. Login to comment 41 ABCG5 p.Gln604Glu ABCG8 p.Thr400Lys ABCG8 p.Tyr54Cys Four SNP sites in ABCG5 Q604E, ABCG8 Y54C, ABCG8 T400K, and ABCG8 A632V were assayed by PCR amplification and RFLP analysis, as previously described [10,11]. Login to comment 42 ABCG8 p.Asp19His Polymorphism of ABCG8 D19H was analyzed using real-time PCR (Taqman MGB assay). Login to comment 72 ABCG5 p.Gln604Glu ABCG5 p.Gln604Glu ABCG8 p.Asp19His ABCG8 p.Asp19His ABCG8 p.Thr400Lys ABCG8 p.Thr400Lys ABCG8 p.Tyr54Cys ABCG8 p.Tyr54Cys Table 2 Linkage disequilibrium in 5 common polymorphisms of ABCG5 and ABCG8 genes D' Locus Q604E D19H Y54C T400K A632V r2 Q604E - 0.368 0.007 0.477 0.087 D19H 0.009 - 0.843 0.718 1.000 Y54C 0.000 0.045 - 0.824 0.211 T400K 0.003 0.000 0.579 - 1.000 A632V 0.000 0.000 0.000 0.001 - D' and r2 were calculated from all 506 subjects in the study. Login to comment 73 ABCG5 p.Gln604Glu ABCG5 p.Gln604Glu ABCG8 p.Asp19His ABCG8 p.Asp19His ABCG8 p.Thr400Lys ABCG8 p.Thr400Lys ABCG8 p.Tyr54Cys ABCG8 p.Tyr54Cys Table 2 Linkage disequilibrium in 5 common polymorphisms of ABCG5 and ABCG8 genes D' Locus Q604E D19H Y54C T400K A632V r2 Q604E - 0.368 0.007 0.477 0.087 D19H 0.009 - 0.843 0.718 1.000 Y54C 0.000 0.045 - 0.824 0.211 T400K 0.003 0.000 0.579 - 1.000 A632V 0.000 0.000 0.000 0.001 - D' and r2 were calculated from all 506 subjects in the study. Login to comment 78 ABCG8 p.Asp19His Because mutation alleles D19H and A632V were rare in this study, the estimated D' values of these alleles and other SNPs may be inflated as suggested by Ardlie et al. [19]. Login to comment 79 ABCG8 p.Asp19His ABCG8 p.Thr400Lys ABCG8 p.Tyr54Cys Thus, only the Y54C and T400K SNPs showed strong linkage disequilibrium (D'N0.8, r2 N1/3) [19]. Login to comment 80 ABCG8 p.Thr400Lys ABCG8 p.Tyr54Cys Thus, only the Y54C and T400K SNPs showed strong linkage disequilibrium (D'N0.8, r2 N1/3) [19]. Login to comment 82 ABCG5 p.Gln604Glu ABCG8 p.Asp19His ABCG8 p.Tyr54Cys No differences were observed when the frequencies of ABCG5 Q604E, ABCG8 D19H, and Y54C and A632V were compared between GS and Table 3 Frequency distribution of the different genotypes and alleles of 5 common ABCG5 and ABCG8 polymorphisms in GS and GSF Polymorphism All (%) Men (%) Women (%) GS GSF GS GSF GS GSF (n=287) (n=219) (n=121) (n=105) (n=166) (n=114) ABCG5:Q604E QQ 78.7 80.4 78.5 78.1 78.9 82.5 QE 20.9 18.7 21.5 20.0 20.5 17.5 EE 0.3 0.9 0 1.9 0.6 0 E allele 10.8 10.3 10.7 11.9 10.8 8.8 OR [95% CI]a 0.95 [0.63~1.42] 1.12 [0.63~2.01] 0.79 [0.45~1.41] ABCG8:D19H DD 98.3 98.6 99.2 99.0 97.6 98.2 DH 1.7 1.4 0.8 1.0 2.4 1.8 HH 0 0 0 0 0 0 H allele 0.9 0.7 0.4 0.5 1.2 0.9 OR [95% CI] 1.27 [0.30~5.36] 0.87 [0.05~13.95] 1.38 [0.25~7.59] ABCG8:Y54C YY 77.4 79.9 76.0 83.8 78.3 76.3 YC 22.3 18.3 24.0 14.3 21.1 21.9 CC 0.3 1.8 0 1.9 0.6 1.8 C allele 11.5 11.0 12.0 9.0 11.1 12.7 OR [95% CI] 1.06 [0.71~1.57] 1.369 [0.74~2.52] 0.861 [0.51~1.45] ABCG8:T400K TT 79.1 83.1 75.2 87.6 81.9 78.9 TK 20.6 16.4 24.8b 12.4 17.5 20.2 KK 0.3 0.5 0 0 0.6 0.9 K allele 10.6 8.7 12.4c 6.2 9.3 11.0 OR [95% CI] 1.25 [0.82~1.92] 2.14 [1.09~4.23] 0.83 [0.48~1.46] ABCG8:A632V AA 99.0 99.1 99.2 100.0 98.8 98.2 AV 1.0 0.9 0.8 0 1.2 1.8 VV 0 0 0 0 0 0 V allele 0.5 0.5 0.4 0 2(0.6) 0.9 OR [95% CI] 0.87 [0.14~5.27] 0.382 [0.02~9.44]d 1.46 [0.20~10.44] a Odds ratio (OR) statistics and 95% confidence intervals (95% CI) were calculated from allele distributions. Login to comment 83 ABCG5 p.Gln604Glu ABCG8 p.Asp19His ABCG8 p.Tyr54Cys No differences were observed when the frequencies of ABCG5 Q604E, ABCG8 D19H, and Y54C and A632V were compared between GS and Table 3 Frequency distribution of the different genotypes and alleles of 5 common ABCG5 and ABCG8 polymorphisms in GS and GSF Polymorphism All (%) Men (%) Women (%) GS GSF GS GSF GS GSF (n=287) (n=219) (n=121) (n=105) (n=166) (n=114) ABCG5:Q604E QQ 78.7 80.4 78.5 78.1 78.9 82.5 QE 20.9 18.7 21.5 20.0 20.5 17.5 EE 0.3 0.9 0 1.9 0.6 0 E allele 10.8 10.3 10.7 11.9 10.8 8.8 OR [95% CI]a 0.95 [0.63~1.42] 1.12 [0.63~2.01] 0.79 [0.45~1.41] ABCG8:D19H DD 98.3 98.6 99.2 99.0 97.6 98.2 DH 1.7 1.4 0.8 1.0 2.4 1.8 HH 0 0 0 0 0 0 H allele 0.9 0.7 0.4 0.5 1.2 0.9 OR [95% CI] 1.27 [0.30~5.36] 0.87 [0.05~13.95] 1.38 [0.25~7.59] ABCG8:Y54C YY 77.4 79.9 76.0 83.8 78.3 76.3 YC 22.3 18.3 24.0 14.3 21.1 21.9 CC 0.3 1.8 0 1.9 0.6 1.8 C allele 11.5 11.0 12.0 9.0 11.1 12.7 OR [95% CI] 1.06 [0.71~1.57] 1.369 [0.74~2.52] 0.861 [0.51~1.45] ABCG8:T400K TT 79.1 83.1 75.2 87.6 81.9 78.9 TK 20.6 16.4 24.8b 12.4 17.5 20.2 KK 0.3 0.5 0 0 0.6 0.9 K allele 10.6 8.7 12.4c 6.2 9.3 11.0 OR [95% CI] 1.25 [0.82~1.92] 2.14 [1.09~4.23] 0.83 [0.48~1.46] ABCG8:A632V AA 99.0 99.1 99.2 100.0 98.8 98.2 AV 1.0 0.9 0.8 0 1.2 1.8 VV 0 0 0 0 0 0 V allele 0.5 0.5 0.4 0 2(0.6) 0.9 OR [95% CI] 0.87 [0.14~5.27] 0.382 [0.02~9.44]d 1.46 [0.20~10.44] a Odds ratio (OR) statistics and 95% confidence intervals (95% CI) were calculated from allele distributions. Login to comment 85 ABCG8 p.Thr400Lys ABCG8 p.Thr400Lys Table 4 Logistic regression analysis All Male Female OR 95% CI P OR 95% CI P OR 95% CI P T400K 1.17 0.73~1.87 NS 2.31 1.12~4.76 0.023 0.70 0.36~1.34 NS Age 0.99 0.97~1.00 NS 0.98 0.96~1.01 NS 0.98 0.96~1.00 0.074 BMI 1.15 1.08~1.23 b0.001 0.99 0.90~1.09 NS 1.30 1.19~1.43 b0.001 Gender 1.50 1.03~2.17 0.033 - - ABCG8 T400K genotypes were coded as 1=the TT genotype and 2=the TK+KK genotype. Login to comment 86 ABCG8 p.Thr400Lys ABCG8 p.Thr400Lys Table 4 Logistic regression analysis All Male Female OR 95% CI P OR 95% CI P OR 95% CI P T400K 1.17 0.73~1.87 NS 2.31 1.12~4.76 0.023 0.70 0.36~1.34 NS Age 0.99 0.97~1.00 NS 0.98 0.96~1.01 NS 0.98 0.96~1.00 0.074 BMI 1.15 1.08~1.23 b0.001 0.99 0.90~1.09 NS 1.30 1.19~1.43 b0.001 Gender 1.50 1.03~2.17 0.033 - - ABCG8 T400K genotypes were coded as 1=the TT genotype and 2=the TK+KK genotype. Login to comment 90 ABCG8 p.Thr400Lys The risk for GS was 2.31 [95% CI 1.12~4.76; P=0.023] for male carrying the K400 allele of ABCG8 T400K, compared to T400 homozygotes after the adjustment for age and BMI. Login to comment 91 ABCG8 p.Thr400Lys The risk for GS was 2.31 [95% CI 1.12~4.76; P=0.023] for male carrying the K400 allele of ABCG8 T400K, compared to T400 homozygotes after the adjustment for age and BMI. Login to comment 93 ABCG8 p.Asp19His For simplicity, the haplotype inference followed the same direction from ABCG5 D19H to ABCG8 A632V which is shown in Table 5. Login to comment 94 ABCG8 p.Asp19His For simplicity, the haplotype inference followed the same direction from ABCG5 D19H to ABCG8 A632V which is shown in Table 5. Login to comment 98 ABCG8 p.Asp19His Plasma and biliary lipid analysis Since the ABCG8 D19H and A632V mutation alleles were rare in our study (frequencyb1%), we only compared plasma and biliary lipid levels between the alleles of the other 3 polymorphisms. Login to comment 99 ABCG5 p.Gln604Glu ABCG8 p.Asp19His ABCG8 p.Tyr54Cys Due to limited number of subjects, heterozygous and homozygous carriers of the genetic variants were combined as follows: ABCG5 Q604E (QE+EE), ABCG8 Y54C (YC+CC), and ABCG8 (TK+KK). Login to comment 100 ABCG5 p.Gln604Glu ABCG8 p.Tyr54Cys Due to limited number of subjects, heterozygous and homozygous carriers of the genetic variants were combined as follows: ABCG5 Q604E (QE+EE), ABCG8 Y54C (YC+CC), and ABCG8 (TK+KK). Login to comment 102 ABCG5 p.Gln604Glu ABCG8 p.Tyr54Cys However, no significant differences were found in the plasma and biliary lipid levels or biliary CSI of subjects with different genotypes of ABCG5 Q604E and ABCG8 Y54C. Login to comment 103 ABCG5 p.Gln604Glu ABCG8 p.Tyr54Cys However, no significant differences were found in the plasma and biliary lipid levels or biliary CSI of subjects with different genotypes of ABCG5 Q604E and ABCG8 Y54C. Login to comment 110 ABCG8 p.Thr400Lys The results indicated that of the five most common polymorphisms in ABCG5 and ABCG8 genes, ABCG8 T400K may be associated with gallstone disease in males. Login to comment 111 ABCG8 p.Thr400Lys The results indicated that of the five most common polymorphisms in ABCG5 and ABCG8 genes, ABCG8 T400K may be associated with gallstone disease in males. Login to comment 115 ABCG8 p.Thr400Lys A, Concentrations of total plasma cholesterol (T-CH), triglycerides (TG), high density lipoprotein cholesterol (HDL-C), and low density lipoprotein cholesterol (LDL-C) between the ABCG8 T400K genotypes in males (n=134). Login to comment 116 ABCG8 p.Thr400Lys ABCG8 p.Thr400Lys B, Concentration (A) of biliary total bile acids (BA), phospholipid (PL), and cholesterol (CH) between the ABCG8 T400K genotypes in males (n=37). Login to comment 117 ABCG8 p.Thr400Lys B, Concentration (A) of biliary total bile acids (BA), phospholipid (PL), and cholesterol (CH) between the ABCG8 T400K genotypes in males (n=37). Login to comment 125 ABCG8 p.Asp19His ABCG8 p.Thr400Lys Berge et al. [11] were the first to report that the ABCG8 D19H and T400K polymorphisms were associated with a lower concentration of plant sterols in both parents and their offspring. Login to comment 126 ABCG8 p.Asp19His ABCG8 p.Thr400Lys Berge et al. [11] were the first to report that the ABCG8 D19H and T400K polymorphisms were associated with a lower concentration of plant sterols in both parents and their offspring. Login to comment 129 ABCG8 p.Thr400Lys It was suggested that the ABCG8 T400K polymorphism influenced the reduction in total plasma cholesterol and LDL cholesterol levels in males, but not in females. Login to comment 130 ABCG8 p.Thr400Lys It was suggested that the ABCG8 T400K polymorphism influenced the reduction in total plasma cholesterol and LDL cholesterol levels in males, but not in females. Login to comment 131 ABCG8 p.Thr400Lys Interestingly, our data showed an association of T400K polymorphism with gallstone disease in male only, a similar gender-specific relationship as in the Czech population. Login to comment 132 ABCG8 p.Thr400Lys Interestingly, our data showed an association of T400K polymorphism with gallstone disease in male only, a similar gender-specific relationship as in the Czech population. Login to comment 147 ABCG8 p.Thr400Lys We speculated that a change from threonine to lysine in the male T400K polymorphism might play a potential role on ABCB4 expression, and thus influence phospholipid secretion. Login to comment 148 ABCG8 p.Thr400Lys We speculated that a change from threonine to lysine in the male T400K polymorphism might play a potential role on ABCB4 expression, and thus influence phospholipid secretion. Login to comment 149 ABCG8 p.Thr400Lys In conclusion, we have demonstrated that the T400K polymorphism in ABCG8 may play a role in the lipid metabolism and formation of gallstones, and may help to predict gallstone disease risk in males, at least within the Chinese population. Login to comment 150 ABCG8 p.Thr400Lys In conclusion, we have demonstrated that the T400K polymorphism in ABCG8 may play a role in the lipid metabolism and formation of gallstones, and may help to predict gallstone disease risk in males, at least within the Chinese population. Login to comment