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

Abstract Objectives Apolipoprotein M plays an important role in the formation of preβ-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.