Role of ATG16L1 Thr300Ala polymorphism in inflammatory bowel disease: a Study in the Spanish population and a meta-analysis.
BACKGROUND
Thr300Ala polymorphism in ATG16L1 was reported as a susceptibility factor to Crohn's disease (CD). Inconsistently replicated associations with ulcerative colitis (UC) and specifically with ileal CD were also reported. Our aims were: to replicate the ATG16L1 Thr300Ala association with inflammatory bowel disease (IBD) in the Spanish population, to perform a meta-analysis to determine the risk conferred to the different IBD subgroups, and to test for the interaction with CARD15 or IL23R risk loci.


METHODS
Thr300Ala (rs2241880) single nucleotide polymorphism (SNP) was genotyped in 712 IBD patients and 745 controls by TaqMan technology. Genetic frequencies were compared with chi-square tests. Our findings were pooled in a meta-analysis.


RESULTS
In Spain, we observed an association of rs2241880 with CD (P = 0.008; odds ratio [OR, 95% confidence interval, CI] = 1.28 [1.06-1.54]), but not with UC. No significant differences emerged when patients were stratified by clinical features. Similarly, the meta-analysis demonstrated a significant association only with CD (P < 10(-4); OR [95% CI] = 1.33 [1.28-1.38]). A significant difference between ileal CD patients and controls was observed, but heterogeneity was found in comparisons involving colonic CD patients and definite conclusions cannot be drawn. No interaction between rs2241880 and the established CARD15 or IL23R susceptibility variants was observed.


CONCLUSIONS
The Thr300Ala polymorphism is associated with CD, regardless of the CARD15 or IL23R status, but not with UC. Stratification by clinical phenotypes did not show definitive results because of the existing heterogeneity among studies.
Márquez
Ana
A
Immunology Department, Hospital Clínico San Carlos, Madrid, Spain.
Núñez
Concepción
C
Martínez
Alfonso
A
Mendoza
Juan Luis
JL
Taxonera
Carlos
C
Fernández-Arquero
Miguel
M
Díaz-Rubio
Manuel
M
de la Concha
Emilio G
EG
Urcelay
Elena
E
D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000453:epidemiology* / Q000235:genetics*; D011110:Polymorphism, Genetic; D013030:Spain / Q000453:epidemiology
C518959:ATG16L1 protein, human; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins