Frequency of MRP1 genetic polymorphisms and their functional significance in Caucasians: detection of a novel mutation G816A in the human MRP1 gene.
OBJECTIVE
The aim of the present study was to determine the frequency of the G816A, T825C, T1684C, and G4002A genetic polymorphisms of the human MRP1 gene in 230 healthy Caucasians. The functional assessment of these mutations was performed in fluorescence-activated cell sorting (FACS)-sorted peripheral blood CD4+ cells in a further 61 healthy volunteers by determining MRP1 mRNA expression.


METHODS
Genotyping of the MRP1 was carried out using real-time polymerase chain reaction (PCR) assays. Quantitative determination of the MRP1 mRNA expression was performed with real-time reverse-transcription-PCR.


RESULTS
A novel silent mutation G816A in exon 8 was found in this study. Allele frequencies of the 816A, 825C, 1684C, and 4002A were 4.1, 30.0, 80.0, and 28.3%, respectively. The frequency of the T825C polymorphism was comparable with that found in a previous Japanese study. In contrast, the frequency of the T1684C (OR 0.06, 95% CI 0.03-0.11, P<0.0001, vs Japanese) and the G4002A (OR 0.47, 95% CI 0.24-0.86, P=0.01, vs Japanese) was significantly rarer. The mean MRP1 mRNA expression in peripheral blood CD4+ cells was 1.03x10(4) +/- 3.8x10(3) molecules/ng of total RNA with an eightfold variation among individuals. However, MRP1 mRNA expression in CD4+ cells was not found to correlate with genetic polymorphisms investigated in this study.


CONCLUSIONS
The genotypic results observed show an ethnic difference in the frequencies of the MRP1 genetic polymorphisms between Japanese and Caucasians. Further studies are required to better understand the clinical consequences of the MRP1 genetic variants.
Oselin
Kersti
K
Institute of Clinical Pharmacology, University Medical Centre Charité, Humboldt University, Berlin, Germany. kersti.oselin@ut.ee
Mrozikiewicz
Przemyslaw M
PM
Gaikovitch
Elena
E
Pähkla
Rein
R
Roots
Ivar
I
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D019742:Chemokines, CC / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D012150:Polymorphism, Restriction Fragment Length; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D044465:White People / Q000235:genetics*
D019742:Chemokines, CC; D012333:RNA, Messenger; C070959:Ccl6 protein, mouse