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

Objectives: Apolipoprotein M plays an important role in the formation of pre beta-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. (C) 2008 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.