Human Genetics

, Volume 120, Issue 6, pp 879–888

Identification of a regulatory SNP in the retinol binding protein 4 gene associated with type 2 diabetes in Mongolia

  • Lkhagvasuren Munkhtulga
  • Kazuhiro Nakayama
  • Nanami Utsumi
  • Yoshiko Yanagisawa
  • Takaya Gotoh
  • Toshinori Omi
  • Maki Kumada
  • Batmunkh Erdenebulgan
  • Khadbaatar Zolzaya
  • Tserenkhuu Lkhagvasuren
  • Sadahiko Iwamoto
Original Investigation

DOI: 10.1007/s00439-006-0264-4

Cite this article as:
Munkhtulga, L., Nakayama, K., Utsumi, N. et al. Hum Genet (2007) 120: 879. doi:10.1007/s00439-006-0264-4

Abstract

Increased levels of retinol binding protein 4 (RBP4) in serum is associated with insulin resistance. To examine this further, the genomic region of RBP4 was genetically surveyed in Mongolian people, who as a group are suffering from a recent rapid increase in diabetes. The RBP4 gene was screened by DHPLC system, and the PCR fragments which showed heteroduplex peaks in multiple samples were followed by direct sequencing to identify common polymorphisms in 48 Mongolian diabetic samples. Identified single nucleotide polymorphisms (SNPs) were genotyped in 511 control and 281 type 2 diabetes samples. The functions of SNPs in the regulatory region were assessed by reporter gene assay and electrophoretic mobility shift assay. Possible association between functional SNPs and serum RBP4 levels or metabolic parameters was statistically assessed. Nine SNPs were identified in the RBP4 gene. A case-control study revealed that the rare alleles of four SNPs were associated with increased risk of diabetes, even after Bonferroni correction (−803, G > A, P = 0.0054; +5169, C > T, P = 0.0025; +6969, G > C, P = 0.0015; +7542, T > del, P = 0.0015). The −803 G > A SNP influenced the transcription efficiency in a hepatocarcinoma cell line as well as the binding efficiency of hepatocyte nuclear factor 1 alpha to the motif. In addition, the −803 A allele was associated with increased serum RBP4 levels in diabetic patients. We have identified a functional SNP in the RBP4 gene associated with type 2 diabetes in Mongolian people.

Abbreviations

RBP4

Retinol binding protein 4

HNF1α

Hepatocyte nuclear factor 1 alpha

SNP

Single nucleotide polymorphism

EMSA

Electrophoretic mobility shift assay

LD

Linkage disequilibrium

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Lkhagvasuren Munkhtulga
    • 1
    • 2
  • Kazuhiro Nakayama
    • 1
  • Nanami Utsumi
    • 1
  • Yoshiko Yanagisawa
    • 1
  • Takaya Gotoh
    • 1
  • Toshinori Omi
    • 1
  • Maki Kumada
    • 1
  • Batmunkh Erdenebulgan
    • 3
  • Khadbaatar Zolzaya
    • 4
  • Tserenkhuu Lkhagvasuren
    • 2
  • Sadahiko Iwamoto
    • 1
  1. 1.Division of Human Genetics, Center for Community MedicineJichi Medical UniversityTochigi Japan
  2. 2.Department of Pathophysiology, Biomedical SchoolHealth Sciences University of MongoliaUlaanbaatarMongolia
  3. 3.Department of Radiology, School of MedicineHealth Sciences University of MongoliaUlaanbaatarMongolia
  4. 4.Department of Endocrinology and Hematology, School of MedicineHealth Sciences University of MongoliaUlaanbaatarMongolia

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