Common NOD2/CARD15 and TLR4 Polymorphisms Are Associated with Crohn's Disease Phenotypes in Southeastern Brazilians.
To investigate whether variants in NOD2/CARD15 and TLR4 are associated with CD and ulcerative colitis (UC) in a genetically admixed population of Rio de Janeiro, where IBD has continued to rise.



We recruited 67 consecutive patients with CD, 61 patients with UC, and 86 healthy and ethnically matched individuals as controls. DNA was extracted from buccal brush samples and genotyped by PCR with restriction enzymes for G908R and L1007finsC NOD2/CARD15 single-nucleotide polymorphisms (SNPs) and for T399I and D299G TLR4 SNPs. Clinical data were registered for subsequent analysis with multivariate models.



NOD2/CARD15 G908R and L1007finsC SNPs were found in one and three patients, respectively, with CD. NOD2/CARD15 G908R and L1007finsC SNPs were not found in any patients with UC, but were found in three and three controls, respectively. With regard to the TLR4 gene, no significant difference was detected among the groups. Overall, none of the SNPs investigated determined a differential risk for a specific diagnosis. Genotype-phenotype associations were found in only CD, where L1007finsC was associated with colonic localization; however, TLR4 T399I SNP was associated with male gender, and D299G SNP was associated with colonic involvement, chronic corticosteroid use, and the need for anti-TNF-alpha therapy.



Variants of NOD2/CARD15 and TLR4 do not confer susceptibility to IBD, but appear to determine CD phenotypes in this southeastern Brazilian population.
Serviço de Gastroenterologia, Departamento de Clínica Médica, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 21941-913, Brazil.
Yolanda F M
YF
Tolentino
Serviço de Gastroenterologia, Departamento de Clínica Médica, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 21941-913, Brazil.
Paula Peruzzi
PP
Elia
Serviço de Gastroenterologia, Departamento de Clínica Médica, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 21941-913, Brazil.
Homero Soares
HS
Fogaça
Serviço de Gastroenterologia, Departamento de Clínica Médica, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 21941-913, Brazil.
Antonio José V
AJ
Carneiro
Serviço de Gastroenterologia, Departamento de Clínica Médica, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 21941-913, Brazil.
Cyrla
C
Zaltman
Instituto de Biologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 21941-590, Brazil.|Instituto Nacional de Metrologia, Qualidade e Tecnologia (INMETRO), Duque de Caxias, Rio de Janeiro, 25250-020, Brazil.
Rodrigo
R
Moura-Neto
Instituto de Estudos de Saúde Coletiva (IESC), Universidade Federal do Rio de Janeiro, Rio de Janeiro, 21944-970, Brazil.
Ronir Raggio
RR
Luiz
Laboratório de Patologia Molecular, Departamento de Patologia, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 21941-913, Brazil.
Maria da Gloria C
Mda G
Carvalho
Serviço de Gastroenterologia, Departamento de Clínica Médica, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 21941-913, Brazil. hsouza@hucff.ufrj.br.|D'Or Institute for Research and Education (IDOR), Rua Diniz Cordeiro 30, Botafogo, Rio de Janeiro, RJ, 22281-100, Brazil. hsouza@hucff.ufrj.br.
Heitor S
HS
de Souza
D000293:Adolescent; D000328:Adult; D000368:Aged; D001938:Brazil; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000235:genetics* / Q000503:physiopathology; D003424:Crohn Disease / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D051197:Toll-Like Receptor 4 / Q000235:genetics*; D055815:Young Adult
C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4
Crohn’s disease; Inflammatory bowel disease; NOD2/CARD15 gene; Single-nucleotide polymorphisms; Toll-like receptor 4 gene