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


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.
Wu
Xiaopan
X
National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, 5 Dongdan 3 Tiao, Beijing 100005, PR China. wuxiaopan1984@tom.com
Niu
Nifang
N
Brismar
Kerstin
K
Zhu
Xilin
X
Wang
Xin
X
Efendic
Suad
S
Du
Te
T
Liu
Yang
Y
Gu
Harvest F
HF
Liu
Ying
Y
D001053:Apolipoproteins / Q000235:genetics* / Q000502:physiology; D000075243:Apolipoproteins M; D044466:Asian People; D002460:Cell Line; D002681:China; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D054834:Lipocalins; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics* / Q000502:physiology; D011401:Promoter Regions, Genetic / Q000235:genetics*; D044465:White People
C400523:APOM protein, human; D001053:Apolipoproteins; D000075243:Apolipoproteins M; D054834:Lipocalins