Polymorphisms in CLEC16A and CIITA at 16p13 are associated with primary adrenal insufficiency.
OBJECTIVE
It is known that different autoimmune diseases often share the same susceptibility genes. In this study we aimed to investigate if loci found associated with common autoimmune diseases in recent genome-wide association studies also could be susceptibility loci for autoimmune Addison's disease (primary adrenal insufficiency).


METHODS
A total of 139 tagging single nucleotide polymorphisms (SNPs) in 11 candidate genes (IL2, IL21, IL2RA, CLEC2D, CD69, ERBB3, PTPN11, SH2B3, CLEC16A, CIITA, and PTPN2) were genotyped in a case/control study design consisting of Norwegian Addison's disease patients (n = 332) and Norwegian healthy control individuals (n = 1029). Five SNPs were subsequently selected for analysis in a United Kingdom sample set consisting of Addison's disease patients (n = 210) and controls (n = 191).


RESULTS
Polymorphisms in CLEC16A and CIITA remained significantly associated with Addison's disease in the Norwegian sample set at the 0.05 level, even after correction for multiple testing. CLEC16A and CIITA are both located at 16p13, but linkage disequilibrium patterns and logistical regression analyses suggest that SNPs in these two genes are independently associated with Addison's disease. We were not able to confirm these associations in the United Kingdom material, however, this may well be due to the limited sample size and lack of statistical power.


CONCLUSIONS
Two alleles at 16p13 are independently associated with the risk of Addison's disease in the Norwegian population, suggesting this chromosomal region to harbor common autoimmunity gene(s), CLEC16A and CIITA being possible independent candidates.
Skinningsrud
Beate
B
Department of Medical Genetics, Ullevål University Hospital, University of Oslo, Kirkeveien 166, N-0407 Oslo, Norway. beate.skinningsrud@medisin.uio.no
Husebye
Eystein S
ES
Pearce
Simon H
SH
McDonald
David O
DO
Brandal
Kristin
K
Wolff
Anette B
AB
Løvås
Kristian
K
Egeland
Thore
T
Undlien
Dag E
DE
D000224:Addison Disease / Q000235:genetics*; D000483:Alleles; D016022:Case-Control Studies; D002885:Chromosomes, Human, Pair 16; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D037181:Lectins, C-Type / Q000235:genetics*; D015810:Linkage Disequilibrium; D009004:Monosaccharide Transport Proteins / Q000235:genetics*; D009664:Norway; D009687:Nuclear Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D015534:Trans-Activators / Q000235:genetics*; D006113:United Kingdom
C522505:CLEC16A protein, human; D037181:Lectins, C-Type; C083728:MHC class II transactivator protein; D009004:Monosaccharide Transport Proteins; D009687:Nuclear Proteins; D015534:Trans-Activators