Identification and Characterization of Single Nucleotide Polymorphisms of SLC22A11 (hOAT4) in Korean Women Osteoporosis Patients

  • Lee, Woon Kyu (Department of Laboratory Animal Medicine, Medical Research Center, College of Medicine, Yonsei University) ;
  • Kwak, Jin Oh (Department of Pharmacology and Toxicology, Inha University) ;
  • Hwang, Ji-Sun (Department of Physiology and Biophysics and Center for Advanced Medical Education by BK21 Project, College of Medicine, Inha University) ;
  • Suh, Chang Kook (Department of Physiology and Biophysics and Center for Advanced Medical Education by BK21 Project, College of Medicine, Inha University) ;
  • Cha, Seok Ho (Department of Pharmacology and Toxicology, Inha University)
  • Received : 2007.10.16
  • Accepted : 2007.10.25
  • Published : 2008.04.30


Single nucleotide polymorphisms (SNPs) are the most common form of human genetic variation. Non-synonymous SNPs (nsSNPs) change an amino acid. Organic anion transporters (OATs) play an important role in eliminating or reabsorbing endogenous and exogenous organic anionic compounds. Among OATs, hOAT4 mediates high affinity transport of estrone sulfate and dehydroepiandrosterone sulfate. The rapid bone loss that occurs in post-menopausal women is mainly due to a net decrease of estrogen. In the present study we searched for SNPs within the exon regions of hOAT4 in Korean women osteoporosis patients. Fifty healthy subjects and 50 subjects with osteoporosis were screened for genetic polymorphism in the coding region of SLC22A11 (hOAT4) using GC-clamp PCR and denaturing gradient gel electrophoresis (DGGE). We found three SNPs in the hOAT4 gene. Two were in the osteoporosis group (C483A and G832A) and one in the normal group (C847T). One of the SNPs, G832A, is an nsSNP that changes the $278^{th}$ amino acid from glutamic acid to lysine (E278K). Uptake of [$3^H$] estrone sulfate by oocytes injected with the hOAT4 E278K mutant was reduced compared with wild-type hOAT4. Km values for wild type and E278K were $0.7{\mu}M$ and $1.2{\mu}M$, and Vmax values were 1.8 and 0.47 pmol/oocyte/h, respectively. The present study demonstrates that hOAT4 variants can causing inter-individual variation in anionic drug uptake and, therefore, could be used as markers for certain diseases including osteoporosis.


Denaturing Gradient Gel Electrophoresis;Estrone Sulfate;GC-Clamp;Human Organic Anion Transporter 4;Osteoporosis;Polymorphism


Supported by : Korea Research Foundation


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