ABCMdb

ABCG8 p.Arg50Cys

None has been submitted yet.

Publications

PMID: 16029460 [PubMed] Rees DC et al: "Stomatocytic haemolysis and macrothrombocytopenia (Mediterranean stomatocytosis/macrothrombocytopenia) is the haematological presentation of phytosterolaemia."

No. Sentence Comment

174 Family Sitosterol level (lmol/l) ABCG5 ABCG8 A E77X (229G>T) A-I-2 44 m/n A-II-1 1471 m/m A-II-2 17 n/n A-II-3 57 n/n A-II-4 970 m/m A-II-5 625 m/m A-II-9 508 m/m B IVS11+3insT R50C (148C>T) E146X (436G>T), M622V (1864A>G) B-I-1 77 n/n m/n B-I-2 42 m/n n/n B-II-1 2230 m/n m/n B-II-2 2350 m/n m/n B-II-3 137 n/n m/n C Q604E (1810C>G) Q271X (811C>T) IV9-3insT IV8-1G/A C54Y (161G>A) C-I-1 114 m/n n/n m/n m/n C-I-2 29 m/m m/n n/n m/m C-II-1 2100 m/n m/n m/n m/n C-II-2 2580 m/n m/n m/n m/n D W361X (1083G>A) D-I-1 22 m/n D-II-1 715 m/m E W361X (1083G>A) E-I-1 23 m/n E-II-1 1844 m/m E-II-2 21 n/n Mutations are shown in bold and large font. Login to comment

PMID: 16507104 [PubMed] Pandit B et al: "A detailed Hapmap of the Sitosterolemia locus spanning 69 kb; differences between Caucasians and African-Americans."

No. Sentence Comment

144 A number of studies have been implicated this locus in disease (or physiologi- Table 4: Results of pair-wise LD analyses Population M1 M2 ChiSq Pval ∆2 D' Caucasian INT1-21 INT1-7 20.01 1E-05 0.545 0.866 5'UTR-19 INT1-7 9.61 0.002 0.256 0.594 Q604E INT1-7 7.14 0.008 0.239 0.489 T400K A632V 6.13 0.013 0.125 1.000 5'UTR-19 T400K 5.84 0.016 0.153 1.000 Q604E D19H 5.02 0.025 0.174 1.000 INT1-7 T400K 4.94 0.026 0.111 1.000 R50C D19H 4.79 0.029 0.234 0.484 INT1-21 T400K 4.45 0.035 0.153 1.000 E238L INT10-50 4.42 0.036 0.238 1.000 INT1-7 C54Y 4.41 0.036 0.138 0.739 5'UTR-19 C54Y 4.24 0.040 0.134 0.619 T400K INT10-50 3.92 0.048 0.040 1.000 5'UTR-19 A565A 3.86 0.049 0.127 1.000 Q604E INT1-21 3.66 0.056 0.128 0.420 INT10-50 A632V 3.29 0.070 0.132 0.641 5'UTR-19 INT1-21 2.86 0.091 0.071 0.267 C54Y T400K 2.74 0.098 0.082 0.433 African-American 5'UTR-19 T400K 11.01 9E-04 0.080 1.000 INT1-7 A565A 8.09 0.004 0.085 0.587 R50C D19H 6.96 0.008 0.205 1.000 T400K A565A 6.56 0.010 0.088 0.557 Q604E INT1-21 5.82 0.016 0.119 0.505 5'UTR-19 A565A 5.10 0.024 0.059 0.460 C54Y A565A 3.93 0.047 0.053 0.270 5'UTR-19 C54Y 3.49 0.062 0.047 0.481 R50C INT1-7 3.05 0.081 0.044 1.000 INT1-7 A632V 3.05 0.081 0.044 1.000 Q604E D19H 3.01 0.083 0.038 1.000 M1 = 1st marker in pair of SNPs, M2 = 2nd marker in pair of SNPs, ChiSq = Value of chi-square test of association, Pval = Two-sided P-value corresponding to chi-square value in ChiSq column assuming 1 degree of freedom. Login to comment
73 Among the unrelated parents (Caucasians) all the SNPs, except R50C were in Hardy-Weinberg Equilibrium (p > 0.005, χ Square test). Login to comment
100 Of note, for the non-synonymous SNPs, R50C and D19H showed some LD in both populations, though the Ch-square statistic was only moderate (Table 4). Login to comment

PMID: 22898925 [PubMed] von Kampen O et al: "Genetic and functional identification of the likely causative variant for cholesterol gallstone disease at the ABCG5/8 lithogenic locus."

No. Sentence Comment

17 Subsequent mutation detection and genotyping yielded two disease-associated variants ABCG5-R50C (p=4.94×10-9 ) and ABCG8-D19H (p=1.74×10-10 ) in high pair-wise LD (r2 =0.95). Login to comment
47 The different versions of both transporters, defined by the respective alleles of R50C and D19H, were introduced by site-directed mutagenesis (QuickChange Lightning Site-Directed Mutagenesis Kit, Agilent Technologies, Santa Clara, CA, USA) according to the Page 10 manufacturer`s protocol. HEK cells were transfected using Effectene Transfection Reagent (Qiagen, Hilden, Germany) according to the manufacturer`s protocol. Login to comment
49 In brief, HEK cells transiently expressing different allelic variants of ABCG5-R50C and ABCG8-D19H were incubated in 24 well cell culture plates with 0.5 ml DMEM supplemented with 10 mM HEPES, pH 7.4, 30 mg/ml cholesterol, 0.5 mCi/ml [³H]-cholesterol and 0.2% fatty acid free BSA for 24 h. Login to comment
79 ABCG8-D19H and ABCG5-R50C are the only functional candidates in the disease interval Owing to the absence of allelic imbalance and allele-dependent splicing, disease mechanisms such as differential transcription efficiency (caused by promoter polymorphisms or variable intronic enhancers) as well as differential transcript structure or stability could be safely ruled out. Login to comment
84 ABCG8-D19H, but not ABCG5-R50C leads to increased cholesterol transport Of all coding SNPs investigated in the disease-associated region, only rs6756629 (ABCG5-R50C; ORallelic=1.96, 95% CI: 1.56-2.47) and rs11887534 (ABCG8-D19H; ORallelic=2.07, 95% CI: 1.65-2.60) were found to be significantly associated with cholelithiasis in our Page 14 mapping panel. Login to comment
98 ABCG8-D19H but not ABCG5-R50C captures the genetic risk across populations In addition to the functional experiments, nested logistic regression analyses were performed to evaluate statistically the causative role of individual variants in the disease-associated region. Login to comment
100 When ABCG5-R50C was included as a mandatory explanatory variable, ABCG8-D19H significantly improved the model fit (p=0.0175) thereby suggesting again that ABCG8-D19H is the major causative variant in the region. Login to comment
101 To confirm this result, rs6756629 (ABCG5-R50C) and rs11887534 (ABCG8-D19H) were also genotyped in additional case-controls samples of German, Chilean, Danish, Indian and Chinese origin (Table 2). Login to comment
103 In each of the samples, ABCG8-D19H consistently showed an equal or higher allelic odds ratio as compared to ABCG5-R50C, thereby supporting the above conclusion. Login to comment