The simultaneous presence of IL-1B and TNFA two-positions risk haplotypes enhances the susceptibility for celiac disease.
To assess the joint contribution of interleukin 1 beta (IL-1B) and tumor necrosis factor alpha (TNFalpha) to the genetic risk of developing celiac disease (CD), we analyzed four biallelic polymorphisms of TNFA and IL-1B genes in 228 patients and 244 healthy controls. The individual contribution of TNFA -308A and IL-1B -511C alleles was weak (OR 1.47 and 1.66, respectively) and was null for TNFA -238 A/G and IL-1B +3953 C/T single nucleotide polymorphisms (SNPs). Due to the potential linkage disequilibrium between TNFA, human leukocyte antigen (HLA) -DQA1 and HLA-DQB1 genes, only individuals carrying DQ2 antigen (DQ2-positive) were considered to perform haplotype analyses. Two-position risk haplotypes were first defined by the combined presence of -511C and +3953T alleles for IL-1B (OR 9.402) or -308A and -238A alleles for TNFA (OR 15.389). The TNFA/IL-1B combined haplotype-stratified association analysis showed that the simultaneous presence of TNFA risk and IL-1B non-risk haplotypes (OR 13.32) but not TNFA non-risk and IL-1B risk haplotypes (OR 0.71) is associated with CD. Interestingly, our data suggest that the coexistence of both risk haplotypes seems to work synergistically (OR 29.59), which enhances the risk of developing CD.
Cherñavsky
Alejandra Claudia
AC
Immunogenetic Laboratory, Hospital de Clínicas José de San Martín, Universidad de Buenos Aires, Av. Cordoba 2351, 1120 Buenos Aires, Argentina. accher@fibertel.com.ar
Páez
María Carolina
MC
Periolo
Natalia
N
Correa
Paula
P
Guillén
Laura
L
Niveloni
Sonia Isabel
SI
Mauriño
Eduardo
E
Bai
Julio César
JC
Anaya
Juan-Manuel
JM
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D002446:Celiac Disease / Q000235:genetics / Q000276:immunology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006683:HLA-DQ Antigens / Q000235:genetics / Q000276:immunology; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; D006239:Haplotypes; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000378:metabolism
D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; C069050:HLA-DQA1 antigen; C069051:HLA-DQB1 antigen; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha