ABCMdb

PMID: 19467940

Tomaiuolo R, Degiorgio D, Coviello DA, Baccarelli A, Elce A, Raia V, Motta V, Seia M, Castaldo G, Colombo C
An MBL2 haplotype and ABCB4 variants modulate the risk of liver disease in cystic fibrosis patients: a multicentre study.
Dig Liver Dis. 2009 Nov;41(11):817-22. Epub 2009 May 20., [PubMed]

Sentences

No. Mutations Sentence Comment

30 ABCC7 p.Gly542* Later, a CF patient homozygous for the G542X mutation was described, who had a severe liver phenotype, unlike the six previously reported cases bearing the same CFTR genotype, who were free of any liver involvement [9]. Login to comment 41 ABCC7 p.Arg553* ABCC7 p.Gly542* ABCC7 p.Glu585* To reduce the possible influence of the CFTR genotype on the liver, we selected only patients who were homozygotes for the F508del mutation (about 80%) or compound heterozygotes for the F508del and another severe (class 1, 2 or 3) CFTR mutation (i.e., c.1717-1G>A; p.G542X; p.NI303K; c.1782delT; c.182delT; c.3659delC; c.4016insT; dele17a-18; p.E585X; p.R553X). Login to comment 64 ABCC7 p.Glu264Val Gene variants CF patients genotypes CF patients alleles With liver disease Without liver disease Fisher p-value With liver disease Withoutliver disease Fisher p-value W.T. het homo W.T. het homo Allele 1 Allele 2 Allele 1 Allele 2 HFE p.H63D 48 14 0 30 14 2 0.14 110 14 74 18 0.12 p.S65C 61 1 0 44 2 0 0.57 123 1 90 2 0.58 p.C282Y 62 0 0 44 2 0 0.18 124 0 90 2 0.18 SPE p.R101H 41 19 0 24 22 0 0.11 101 19 70 22 0.16 p.V213A 45 14 1 28 16 2 0.26 104 16 72 20 0.14 p.D256D 59 1 0 46 0 0 1.00 119 1 92 0 1.00 p.E264V 60 0 0 44 2 0 0.18 120 0 90 2 0.19 p.E376D 40 17 3 30 15 1 0.77 97 23 75 17 1.00 ABCB4 c.287-61C>T 56 0 0 40 6 0 0.52 112 0 86 6 0.54 c.351A>T 31 1 0 45 1 0 1.00 63 1 91 1 1.00 c.504T>C 17 38 6 17 17 12 0.017 72 50 51 41 0.68 c.523A>G 59 2 0 46 0 0 0.50 120 2 92 0 0.51 c.711A>T 47 13 1 27 18 1 0.08 107 15 72 20 0.09 c.834-66G>T 48 13 0 27 18 1 0.04 109 13 72 20 0.03 c.1005+7A>C 60 1 0 46 0 0 1.00 121 1 92 0 1.00 c.1005+41T>G 60 1 0 46 0 0 1.00 121 1 92 0 1.00 c.1357-40G>A 53 7 1 38 8 0 0.57 113 9 84 8 0.80 c.1529A>G 61 0 0 45 1 0 0.43 122 0 91 1 0.43 c.1732-39A>G 54 0 0 36 1 0 0.41 108 0 73 1 0.41 c.1893+34G>C 53 1 0 37 0 0 1.00 107 1 74 0 1.00 c.1954A>G 48 13 0 41 5 0 0.20 109 13 87 5 0.22 c.2064+55A>G 48 13 0 41 5 0 0.20 109 13 87 5 0.22 c.2211+16T>C 53 7 1 39 7 0 0.87 113 9 85 7 1.00 c.2478+40A>G 49 11 0 40 5 0 0.41 109 11 85 5 0.43 c.2479-67delG 49 12 0 38 5 0 0.42 110 12 81 5 0.44 c.2555A>G 61 1 0 45 1 0 0.43 123 1 91 1 0.43 c.3508-88T>C 61 1 0 45 1 0 0.43 123 1 91 1 0.43 c.3508-16C>T 52 7 1 37 9 0 0.34 111 9 83 9 0.62 c.3655-72T>C 49 12 0 40 5 0 0.29 110 12 85 5 0.31 wt: wild type; het: heterozygotes; homo: homozygotes; significantly different results are reported in bold. Login to comment 74 ABCB4 p.Thr175Ala Among them, we observed the already described hypomorphic allele c.523A>G (p.T175A) in heterozygous state in two CF patients with cirrhosis. Login to comment 75 ABCB4 p.Thr175Ala Among them, we observed the already described hypomorphic allele c.523A>G (p.T175A) in heterozygous state in two CF patients with cirrhosis. Login to comment 98 ABCC7 p.Glu264Val ABCC7 p.Glu264Val Similarly, we did not find differences in the frequency of the p.E264V mutation of SPE gene between CF patients with and without liver disease; furthermore, none of the subjects of our study had the other SPE mutation (i.e., p.E342K) that together to p.E264V causes the A1AT deficient phenotype [37]. Login to comment 111 ABCB4 p.Thr175Ala Among these the hypomorphic allele c.523A>G (p.T175A), the most common ABCB4 mutation, segregates with two CF patients with cirrhosis, and is absent in all CF patients without liver disease. Login to comment 112 ABCB4 p.Thr175Ala Among these the hypomorphic allele c.523A>G (p.T175A), the most common ABCB4 mutation, segregates with two CF patients with cirrhosis, and is absent in all CF patients without liver disease. Login to comment 113 ABCB4 p.Thr175Ala Indeed, the ABCB4 allele p.T175A has been recently reported as a disease-causing mutation in three subjects with PFIC3 phenotype [24]. Login to comment 114 ABCB4 p.Thr175Ala ABCB4 p.Thr175Ala Indeed, the ABCB4 allele p.T175A has been recently reported as a disease-causing mutation in three subjects with PFIC3 phenotype [24]. Login to comment 115 ABCB4 p.Thr175Ala Further studies on a larger number of patients are needed to establish the role of p.T175A allele in predisposing to liver disease in CF patients. Login to comment