Apolipoprotein M promoter polymorphisms alter promoter activity and confer the susceptibility to the development of type 1 diabetes

Clin Biochem. 2009 Jan;42(1-2):17-21. doi: 10.1016/j.clinbiochem.2008.10.008. Epub 2008 Oct 30.

Abstract

Objectives: Apolipoprotein M plays an important role in the formation of prebeta-HDL and cholesterol efflux to HDL. In the present study, we investigate the potential association between the ApoM promoter polymorphisms and type 1 diabetes.

Design and methods: The study was conducted in Peking Union Medical College, Beijing, China and Karolinska Institutet, Stockholm, Sweden. Two populations, including 493 Han Chinese subjects (177 T1D patients/316 controls) and 225 Swedish (124/101), are enrolled in the present study. Three single nucleotide polymorphisms (SNP) C-1065A, T-855C and T-778C in the promoter region of the ApoM gene are genotyped using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) protocol. Promoter activity was measured by reporter gene assay.

Results: SNP T-778C was strongly associated with T1D in both Han Chinese (p=0.002, OR=2.188, CI 95%=1.338-3.581) and Swedish (p=0.021, OR=2.865, CI 95%=1.128-7.278) populations. The luciferase activity of -778C promoter was 1.41 times as high as that of -778T promoter (9.90+/-1.92 vs. 7.04+/-0.76, p=0.001).

Conclusions: Allele C of SNP T-778C may increase promoter activity and confer the risk susceptibility to the development of T1D.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apolipoproteins / genetics*
  • Apolipoproteins / physiology
  • Apolipoproteins M
  • Asian People
  • Cell Line
  • China
  • Diabetes Mellitus, Type 1 / epidemiology
  • Diabetes Mellitus, Type 1 / genetics*
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Lipocalins
  • Polymerase Chain Reaction
  • Polymorphism, Restriction Fragment Length / genetics
  • Polymorphism, Single Nucleotide / genetics*
  • Polymorphism, Single Nucleotide / physiology
  • Promoter Regions, Genetic / genetics*
  • White People

Substances

  • APOM protein, human
  • Apolipoproteins
  • Apolipoproteins M
  • Lipocalins