Confirmation of an association between rs6822844 at the Il2-Il21 region and multiple autoimmune diseases: evidence of a general susceptibility locus.
OBJECTIVE
Autoimmune diseases often have susceptibility genes in common, indicating similar molecular mechanisms. Increasing evidence suggests that rs6822844 at the IL2-IL21 region is strongly associated with multiple autoimmune diseases in individuals of European descent. This study was undertaken to attempt to replicate the association between rs6822844 and 6 different immune-mediated diseases in non-European populations, and to perform disease-specific and overall meta-analyses using data from previously published studies.


METHODS
We evaluated case-control associations between rs6822844 and celiac disease (CD) in subjects from Argentina; rheumatoid arthritis (RA), type 1 diabetes mellitus (DM), primary Sjögren's syndrome (SS), and systemic lupus erythematosus (SLE) in subjects from Colombia; and Behçet's disease (BD) in subjects from Turkey. Allele and gene distributions were compared between cases and controls. Meta-analyses were performed using data from the present study and previous studies.


RESULTS
We detected significant associations of rs6822844 with SLE (P = 0.008), type 1 DM (P = 0.014), RA (P = 0.019), and primary SS (P = 0.033) but not with BD (P = 0.34) or CD (P = 0.98). We identified little evidence of population differentiation (F(ST) = 0.01) within cases and controls from Argentina and Colombia, suggesting that association was not influenced by population substructure. Disease-specific meta-analysis indicated significant association for RA (P(meta) = 3.61 x 10(-6)), inflammatory bowel disease (IBD; Crohn's disease and ulcerative colitis) (P(meta) = 3.48 x 10(-12)), type 1 DM (P(meta) = 5.33 x 10(-5)), and CD (P(meta) = 5.30 x 10(-3)). Overall meta-analysis across all autoimmune diseases reinforced association with rs6822844 (23 data sets; P(meta) = 2.61 x 10(-25), odds ratio 0.73 [95% confidence interval 0.69-0.78]).


CONCLUSIONS
Our results indicate that there is an association between rs6822844 and multiple autoimmune diseases in non-European populations. Meta-analysis results strongly reinforce this robust association across multiple autoimmune diseases in both European-derived and non-European populations.
Maiti
Amit K
AK
Oklahoma Medical Research Foundation, Oklahoma City, OK73104, USA.
Kim-Howard
Xana
X
Viswanathan
Parvathi
P
Guillén
Laura
L
Rojas-Villarraga
Adriana
A
Deshmukh
Harshal
H
Direskeneli
Haner
H
Saruhan-Direskeneli
Güher
G
Cañas
Carlos
C
Tobön
Gabriel J
GJ
Sawalha
Amr H
AH
Cherñavsky
Alejandra C
AC
Anaya
Juan-Manuel
JM
Nath
Swapan K
SK
D001118:Argentina / Q000453:epidemiology; D001172:Arthritis, Rheumatoid / Q000208:ethnology / Q000235:genetics; D001327:Autoimmune Diseases / Q000208:ethnology* / Q000235:genetics*; D016022:Case-Control Studies; D003105:Colombia / Q000453:epidemiology; D003922:Diabetes Mellitus, Type 1 / Q000208:ethnology / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000208:ethnology; D005838:Genotype; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics*; D007378:Interleukins / Q000235:genetics*; D008180:Lupus Erythematosus, Systemic / Q000208:ethnology / Q000235:genetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012859:Sjogren's Syndrome / Q000208:ethnology / Q000235:genetics; D014421:Turkey / Q000453:epidemiology; D000098546:Interleukin-21
D007376:Interleukin-2; D007378:Interleukins; D000098546:Interleukin-21