ABCMdb

PMID: 19998509

Chen XQ, Wang LL, Shan QW, Tang Q, Lian SJ
Multidrug resistance protein 3 R652G may reduce susceptibility to idiopathic infant cholestasis.
World J Gastroenterol. 2009 Dec 14;15(46):5855-8., [PubMed]

Sentences

No. Mutations Sentence Comment

7 ABCB4 p.Arg652Gly Polymerase chain reaction was used to amplify the multidrug resistance protein 3 (MDR3) R652G fragment, and products were sequenced using the ABI 3100 Sequencer. Login to comment 8 ABCB4 p.Arg652Gly RESULTS: The R652G single nucleotide polymorphism (SNP) was significantly more frequent in healthy infants (allele frequency 8.0%) than in patients (allele frequency 2.60%) (P < 0.05), odds ratio, 0.29; 95% confidence interval, 0.12-0.84. Login to comment 10 ABCB4 p.Arg652Gly CONCLUSION: MDR3 R652G is negatively correlated with idiopathic infant cholestasis. Login to comment 11 ABCB4 p.Arg652Gly Children with the R652G SNP in Guangxi of China may have reduced susceptibility to infant intrahepatic cholestasis. Login to comment 13 ABCB4 p.Arg652Gly Key words: Multidrug resistance protein 3; Single nucleotide polymorphisms; R652G; Infant; Cholestasis Peer reviewer: Tamara Alempijevic, MD, PhD, Assistant Professor, Clinic for Gastroenterology and Hepatology, Clinical Centre of Serbia, 2 Dr Koste Todorovica St., Belgrade 11000, Serbia Chen XQ, Wang LL, Shan QW, Tang Q, Lian SJ. Login to comment 14 ABCB4 p.Arg652Gly Multidrug resistance protein 3 R652G may reduce susceptibility to idiopathic infant cholestasis. World J Gastroenterol 2009; 15(46): 5855-5858 Available from: URL: http://www.wjgnet.com/1007-9327/15/ 5855.asp DOI: http://dx.doi.org/10.3748/wjg.15.5855 INTRODUCTION Idiopathic infant cholestasis is of unknown etiology and can occur in either a sporadic or a familial form. Login to comment 18 ABCB4 p.Arg652Gly Studies have investigated the involvement of MDR3 variants in the development of disease, and we were interested to note that the MDR3 R652G single nucleotide polymorphism (SNP) has a high allele frequency in generally healthy people[7] . Login to comment 19 ABCB4 p.Arg652Gly Our aim was to study the MDR3 R652G SNP distribution frequency in idiopathic infant cholestasis and healthy infants and to determine whether there were any differences between them and, if so, their relevance. Login to comment 24 ABCB4 p.Arg652Gly Polymerase chain reaction (PCR) amplified the MDR3 R652G and sequence analysis Genomic DNA was extracted from peripheral venous blood leukocytes using standard phenol chloroform procedures. Login to comment 26 ABCB4 p.Arg652Gly Primers for MDR3 R652G were forward (5'-CATCCATTTGGAGACACACACAC-3') and reverse (5'-GTAGCAGTCATCTGTGCCTGAA A-3')[7] . Login to comment 27 ABCB4 p.Arg652Gly The primary PCR product fragments were 348 bp. PCRs for generating the R652G fragments were generally performed in a reaction volume of 50 μL with 100 ng of genomic DNA, 1.5 U of Taq polymerase (Fermentas), 10 × PCR buffer (Fermentas), 1.5 mmol/L of MgCl2 (Fermentas), 200 μmol/L deoxynucleoside- 5-triphosphate (Takara) and 20 μmol of each primer. Login to comment 32 ABCB4 p.Arg652Gly Comparison of the frequency of the R652G SNP was made between patients and controls, and the analysis of association with the phenotype was performed by χ 2 test or Fisher`s exact test when appropriate. Login to comment 44 ABCB4 p.Arg652Gly PCR products sequence analysis showed a heterozygous substitution A>G (Figure 1) in codon 652 which creates an amino acid substitution in codon R652G in exon 16. Login to comment 46 ABCB4 p.Arg652Gly Test results showed that the R652G genotype distribution in the 2 groups was in line with the Hardy-Weinberg equilibrium, indicating that the selected sample was representative of the population. Login to comment 51 ABCB4 p.Arg652Gly Table 2 MDR3 R652G genotypes and allele frequencies in patients and controls n (%) Groups n Genotypes Allele P-value A/A A/G G/G frequency (%) Patients 78 74 (94.9) 4 (5.1) 0 2.6 < 0.051 Controls 113 95 (84.1) 18 (15.9) 0 8.0 1 Fisher`s exact test between patients and controls for genotype frequency. Login to comment 53 ABCB4 p.Arg652Gly A A G G C T G C C A C T N G A A T G G C C C C A A A Figure 1 Sequence of the multidrug resistance protein-3 (MDR3) single nucleotide polymorphism R652G (A>G). Login to comment 57 ABCB4 p.Arg652Gly DISCUSSION Our study is the first report of the MDR3 R652G SNP in children in China. Login to comment 58 ABCB4 p.Arg652Gly Our data showed that the R652G SNP had a significantly higher proportional distribution in normal infants than in idiopathic infant cholestasis patients. Login to comment 61 ABCB4 p.Arg652Gly For this reason, we can infer that the R652G variant has a specific protective effect in the normal population. Login to comment 62 ABCB4 p.Arg652Gly In previous studies, in the analysis of MDR3 gene sequence variants in different countries, the R652G SNP was the only protein-altering variant with high allele frequency in all groups. Login to comment 65 ABCB4 p.Arg652Gly R652G is a MDR3 gene mutation that results in non-synonymous amino acid substitutions but is not associated with disease. Login to comment 66 ABCB4 p.Arg652Gly In Switzerland, a study showed that the MDR3 R652G variant was 7% in healthy Caucasians, 9% in drug-induced cholestatic patients and 4% in hepatocellular/mixed liver injury[9] . Login to comment 67 ABCB4 p.Arg652Gly Pauli-Magnus et al[10] reported the R652G variant in 10% of intrahepatic cholestasis pregnancy cases and 16.3% in healthy controls. Login to comment 68 ABCB4 p.Arg652Gly The previous studies indicated that the R652G variant was prevalent in the general population. Login to comment 69 ABCB4 p.Arg652Gly ABCB4 p.Arg652Gly Furthermore, studies of MDR3 R652G in a variety of diseases showed no evidence that the R652G variant was related to disease. Login to comment 70 ABCB4 p.Arg652Gly In our study, the R652G variant was 15.9% in healthy children, with a higher frequency than in infant cholestasis patients. Login to comment 73 ABCB4 p.Arg652Gly There is also another phenomenon whereby R652G may have a protective effect and reduce the risk of suffering from disease. Login to comment 74 ABCB4 p.Arg652Gly Jacquemin et al[11] reported one patient with intrahepatic cholestasis of pregnancy carrying a R652G substitution, and whose biliary phospholipids were lower than other patients. Login to comment 78 ABCB4 p.Arg652Gly A recent study of gallstones in sibling pairs and controls showed that R652G variant frequency was 18% in patients and 25% in controls. Login to comment 88 ABCB4 p.Arg652Gly In conclusion, the MDR3 R652G SNP is negatively correlated with cholestasis (OR, 0.29, 95% CI, 0.12-0.84). Login to comment 89 ABCB4 p.Arg652Gly Children in Guangxi of China with the R652G variant may have reduced susceptibility to infant intrahepatic cholestasis. Login to comment 94 ABCB4 p.Arg652Gly However, an interesting phenomenon is that there was no positive evidence for the MDR3 R652G variant being involved in the pathogenesis of intrahepatic cholestasis. Login to comment 95 ABCB4 p.Arg652Gly This study investigated the MDR3 R652G distributed allele frequency in idiopathic infant cholestasis and healthy infants to determine whether there were any difference and, if so, their relevance. Login to comment 98 ABCB4 p.Arg652Gly ABCB4 p.Arg652Gly In order to evaluate the role of the MDR3 R652G variant in the pathogenesis of idiopathic infant cholestasis, the authors analyzed the MDR3 R652G polymorphism in a case-control study in Guangxi Chinese infants. Login to comment 99 ABCB4 p.Arg652Gly The authors found that the R652G variant was significantly more frequent in healthy infants than in patients. Login to comment 100 ABCB4 p.Arg652Gly The results showed that the R652G variant has a protective effect in healthy infants and reduces the possibility of suffering from idiopathic infant cholestasis. Login to comment 104 ABCB4 p.Arg652Gly MDR3 R652G and infant intrahepatic cholestasis was not the same as a previous study. Login to comment 106 ABCB4 p.Arg652Gly Applications The study results suggest that the MDR3 R652G variant has a protective effect in healthy infants. Login to comment 107 ABCB4 p.Arg652Gly This will give further information for comparing geographical regions, and it is very important to establish particular characteristics of MDR3 R652G that can be useful in the differential diagnosis of idiopathic infant cholestasis, and furthermore, may establish the influence of such an single nucleotide polymorphism (SNP) in prognosis. Login to comment 108 ABCB4 p.Arg652Gly ABCB4 p.Arg652Gly Terminology MDR3 R652G: MDR3 R652G is a SNP of the MDR3 in the 652 coding site. Login to comment 110 ABCB4 p.Arg652Gly ABCB4 p.Arg652Gly The R652G is a gene mutation where the adenine (A) mutates into guanine (G) which causes AGA>GGA resulting in arginine substitution by glycine (R652G). Login to comment