ABCMdb

ABCB4 p.Gly536Arg

None has been submitted yet.

Publications

PMID: 18083082 [PubMed] Floreani A et al: "Hepatobiliary phospholipid transporter ABCB4, MDR3 gene variants in a large cohort of Italian women with intrahepatic cholestasis of pregnancy."

No. Sentence Comment

54 The median peak serum transaminases were 114.6 U/L (range 42-1117) and 164.5 U/L (range 47-1186) for AST Table 2 Clinical details of the patients with ICP N = 96 (%) Median age (range) 34 years (19-47) Parity 0001 68 70.8 0002 22 22.9 0003 6 6.3 Family history of ICP 8 8.3 Median AST (U/L; range) 114.6 (42-1117) Median ALT (U/L; range) 164.5 (47-1186) 10.4 Median total bile salts (␮M; range) 14.35 (3-115) Total bile salts >40 ␮M 10 10.4 Median total bilirubin (mg/dL) 0.61 (0.23-2.35) Abnormal bilirubin 10 11.4 Median serum GGT (U/L; range) 20.5 (4-147) Abnormal serum GGT 11 Normal values: AST, aspartate aminotransferase <40 U/L; ALT, alanine transferase <45 U/L; total bile salts <2 ␮M. Table 3 Polymorphisms of exons 14, 15 and 16 found in the study population cDNA (exon) N refer N var AA change 1584 (14) G C E528D 1606 (14) G A G536R 1646 (14) G A R549H 1769 (15) G A R590Q 1954 (16) A G R652G 2000 (16) C T T667I andALTrespectively.Eighty-sixpatientshadbilirubinwithin the normal range, while 10 (10.4%) had a slight rise in total bilirubin (2-3 mg/dL). Login to comment
56 Sequence analysis of exon 14 revealed the three heterozygous mutations previously described: (1) the GAG-GAC mutation in codon 528, resulting in the substitution of the wild-type glutamic acid with a mutant aspartic acid (E528D); (2) a CGC-CAC mutation in codon 549, resulting in the substitution of the wild-type arginine with mutant histidine (R549H); (3) the GGG-AGG mutation in codon 536 resulting in the substitution of the wild-type glycine with mutant arginine (G536R) (Table 3). Login to comment
57 Sequence analysis of exon 15 showed an heterozygous mutation in codon 590 with a consequent substitution of the wild-type arginine with glutamine (R590Q). Login to comment
80 There is a difference, however, in the phenotypic expression of this condition by comparison Table 4 Clinical details of ICP patients with MDRR3 mutations Patient #1 E528D Patient #2 R549H Patient #3 G536R Patient #4 R590Q Patient #5 R652G Patient #6 T667I Patient #7 R652G Onset of pruritus 3rd trimester 3rd trimester 3rd trimester 3rd trimester 3rd trimester 3rd trimester 3rd trimester Parity 0002 0001 0001 0001 0001 0001 0001 Previous ICP No Yes Yes No No No No Peak of AST (U/L) 163 88 129 62 789 119 60 Peak of ALT (U/L) 98 121 137 88 1186 125 78 Bilirubin (mg/dL) 0.60 0.61 0.89 1.2 0.57 0.3 0.78 Peak of GGT (U/L) 8 15 19 10 25 35 5 Cholesterol lithiasis No No Yes No No No No Total bile salts (␮M/L) 3.3 6.3 10.1 60 76.3 25.3 4.0 Delivery Vaginal Vaginal Caesarean Vaginal Caesarean Caesarean Vaginal ICP, intrahepatic cholestasis of pregnancy; AST, aspartate aminotransferase; ALT, alanine aminotransferase. Login to comment
55 Table 3 Polymorphisms of exons 14, 15 and 16 found in the study population cDNA (exon) N refer N var AA change 1584 (14) G C E528D 1606 (14) G A G536R 1646 (14) G A R549H 1769 (15) G A R590Q 1954 (16) A G R652G 2000 (16) C T T667I andALTrespectively.Eighty-sixpatientshadbilirubinwithin the normal range, while 10 (10.4%) had a slight rise in total bilirubin (2-3 mg/dL). Login to comment
81 There is a difference, however, in the phenotypic expression of this condition by comparison Table 4 Clinical details of ICP patients with MDRR3 mutations Patient #1 E528D Patient #2 R549H Patient #3 G536R Patient #4 R590Q Patient #5 R652G Patient #6 T667I Patient #7 R652G Onset of pruritus 3rd trimester 3rd trimester 3rd trimester 3rd trimester 3rd trimester 3rd trimester 3rd trimester Parity 0002 0001 0001 0001 0001 0001 0001 Previous ICP No Yes Yes No No No No Peak of AST (U/L) 163 88 129 62 789 119 60 Peak of ALT (U/L) 98 121 137 88 1186 125 78 Bilirubin (mg/dL) 0.60 0.61 0.89 1.2 0.57 0.3 0.78 Peak of GGT (U/L) 8 15 19 10 25 35 5 Cholesterol lithiasis No No Yes No No No No Total bile salts (òe;M/L) 3.3 6.3 10.1 60 76.3 25.3 4.0 Delivery Vaginal Vaginal Caesarean Vaginal Caesarean Caesarean Vaginal ICP, intrahepatic cholestasis of pregnancy; AST, aspartate aminotransferase; ALT, alanine aminotransferase. Login to comment

PMID: 16696816 [PubMed] Floreani A et al: "Intrahepatic cholestasis of pregnancy: three novel MDR3 gene mutations."

No. Sentence Comment

6 Results Three novel non-synonymous heterozygous mutations in exon 14 were found (4%; E528D, R549H, G536R) among the 80 intrahepatic cholestasis of pregnancy patients, whereas the pregnant controls were all negative for exon 14 polymorphisms. Login to comment
51 Patient #3 had a heterozygous mutation (GGG-AGG) in codon 536 with a consequent substitution of the wild-type glycine with mutant arginine (G536R). Login to comment
68 ATP-binding and hydrolysis are mediated by NBDs, which are characterized as in all ABC transporters, by three consensus motifs: the Walker A, Walker B and a linker region (ABC signature dodecapeptide) just upstream from the Walker B domain).10 The G536R mutation is located in the linker region of the NBD1. Login to comment
72 Patient #1 E528D mutation Patient #3 G536R mutation Patient #2 R549H mutation Figure 1. Login to comment
75 Clinical details of ICP patients with heterozygous mutations Patient #1 E528D Patient #2 R549H Patient #3 G536R Onset of pruritus 3rd trimester 3rd trimester 3rd trimester Parity 0002 0001 0001 Previous ICP No Yes Yes Peak of AST (U/L) 163 88 129 Peak of ALT (U/L) 98 121 137 Bilirubin (mg/dL) 0.60 0.61 0.89 Peak of GGT (U/L) 8 15 19 Cholesterol lithiasis No Yes No Total bile salts (lM/L) 3.3 6.3 10.1 Delivery Vaginal Vaginal Caesarean ICP, intrahepatic cholestasis of pregnancy; AST, aspartate aminotransferase; ALT, alanine aminotransferase. A drawback of our study lies is not having sequenced the whole MDR3 gene, as our study design only involved sequencing exon 14; may also consequently underestimate the real prevalence of MDR3 mutations in ICP patients. Login to comment