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KMID : 0811720070110000081
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Korean Journal of Physiology & Pharmacology
2007 Volume.11 No. 0 p.81 ~ p.0
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Genetic Diversity of the Human Organic Anion Transporter 4 Gene in Korean Osteoporosis or Rheumatoid Arthritis Patients
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Cha Seok-Ho
Kwak Jin-Oh
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Abstract
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In order to clarify the genetic variation of human organic anion transporter 4 (hOAT4), the genetic feature of the hOAT4 coding region was investigated using denaturing gradient gel electrophoresis in 50 patients with osteoporosis (OP), 44 patients with rheumatoid arthritis (RA) and normal person (CTL) counterpart against each patients was compared with 50 and 40 persons, respectively. The functional analysis of found single nucleotide polymorpohims (SNPs) was done by the Xenopus laevis oocyte expression system. The five SNPs (C483A, G832A, C847T, T566C and T1292C) in the OP, RA and each CTL group by the duplex PCR were found and their sequences were analyzed in the hOAT4 coding region. Among them, The G832A polymorphism was the only one reported in National Center for Biotechnology Information (NCBI) and the others are the novel SNPs. The C483A and G832A polymorphisms were identified in the OP group and the C847T polymorphism was in OP-CTL group. The C483A and G832A polymorphisms were detected in the RA group, whereas the T566C and T1292C polymorphisms were in RA-CTL group. In addition, the G832A polymorphism was a non-synonymous SNP which altered the 278th amino acid sequence from glutamic acid (E) to lysine (K). To examine the function of the found SNP, the cDNA variant was constructed and expressed in X. laevis oocytes. The [3H]-estrone sulfate uptake profile of hOAT4 and constructed mutant was investigated. The uptake of [3H]-estrone sulfate (100 nM), the G832A, was significantly decreased in G832A nsSNP group. In addition, The Km and Vmax values for the uptake differed between wild type hOAT4 (0.7μM and 1.7 pmol/oocyte/hr, respectively) and G832A nsSNP mutant (2.0μM and 0.6 pmol/oocyte/hr, respectively). Based on these results, the hOAT4 variant (G832A) affected the Km and Vmax values of hOAT4, and significantly decreased the uptake of the estrone sulfate substrate.
Source: Korean Journal of Physiology & Pharmacology.2007 Oct;11(Suppl II):S79-S79
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KEYWORD
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Organic anion transporter 4 (hOAT4), Single nucleotide polymorphism (SNP), Osteoporosis, Rheumatoid arthritis, Estrone sulfate
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