RESUMO
BACKGROUND: DLG5 p.R30Q has been reported to be associated with Crohn disease (CD), but this association has not been replicated in most studies. A recent analysis of gender-stratified data from two case-control studies and two population cohorts found an association of DLG5 30Q with increased risk of CD in men but not in women and found differences between 30Q population frequencies for males and females. Male-female differences in population allele frequencies and male-specific risk could explain the difficulty in replicating the association with CD. METHODS: DLG5 R30Q genotype data were collected for patients with CD and controls from 11 studies that did not include gender-stratified allele counts in their published reports and tested for male-female frequency differences in controls and for case-control frequency differences in men and in women. RESULTS: The data showed no male-female allele frequency differences in controls. An exact conditional test gave marginal evidence that 30Q is associated with decreased risk of CD in women (p = 0.049, OR = 0.87, 95% CI 0.77 to 1.00). There was also a trend towards reduced 30Q frequencies in male patients with CD compared with male controls, but this was not significant at the 0.05 level (p = 0.058, OR = 0.87, 95% CI 0.74 to 1.01). When data from this study were combined with previously published, gender-stratified data, the 30Q allele was found to be associated with decreased risk of CD in women (p = 0.010, OR = 0.86, 95% CI 0.76 to 0.97), but not in men. CONCLUSION: DLG5 30Q is associated with a small reduction in risk of CD in women.
Assuntos
Alelos , Doença de Crohn/genética , Frequência do Gene , População Branca/genética , Estudos de Casos e Controles , Doença de Crohn/etnologia , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Proteínas de Membrana/genética , Razão de Chances , Fatores Sexuais , Proteínas Supressoras de Tumor/genéticaRESUMO
The region on chromosome 6 encoding the major histocompatibility complex (MHC) is associated with a number of autoimmune and infectious diseases. Primary susceptibility to many of these has been localized to a region containing the human leukocyte antigen (HLA)-DR and -DQ genes. A recent study of sarcoidosis has provided evidence of an independent effect, associated with a truncating single nucleotide polymorphism (SNP) of a nearby gene, BTNL2. This gene may encode an immune receptor involved in costimulation. Sarcoidosis, tuberculoid leprosy, tuberculosis (TB) and Crohn's disease all have similar immunological features, including a Th1 response with granuloma formation. In addition mycobacteria have been identified or suggested to be causative pathogens in such conditions. We genotyped the truncating BTNL2 SNP in 92 TB and 72 leprosy families from Brazil and carried out family-based association studies. We could not find evidence of overtransmission of the truncating allele in TB. There was an association with susceptibility to leprosy (P=0.04), however, this is most likely due to linkage disequilibrium with HLA-DR. We also genotyped 476 UK Caucasian cases of Crohn's disease with 760 geographically matched controls and found no evidence of a disease association. We conclude that the truncating BTNL2 SNP is not important in this group of Th1 dominated granulomatous diseases.
Assuntos
Doença de Crohn/genética , Hanseníase/genética , Glicoproteínas de Membrana/genética , Mutação Puntual , Polimorfismo de Nucleotídeo Único , Sítios de Splice de RNA/genética , Tuberculose/genética , Alelos , Brasil , Butirofilinas , Cromossomos Humanos Par 6/genética , Feminino , Antígenos HLA-DQ/genética , Antígenos HLA-DR/genética , Humanos , Desequilíbrio de Ligação , Masculino , Reino UnidoRESUMO
BACKGROUND AND AIMS: Genetic association between Crohn's disease (CD) and OCTN1 (SLC22A4) C1672T/OCTN2 (SLC22A5) G-207C variants in IBD5 has recently been reported. These genes encode solute carriers and the association was suggested to be distinct from the background IBD5 risk haplotype. There have been conflicting reports of the association between markers in the IBD5 region and ulcerative colitis (UC) and interaction (epistasis) between this locus and CARD15. Our aim was to ascertain the contribution of OCTN variants to UC and CD in a large independent UK dataset, to seek genetic evidence that the OCTN association is distinct from the IBD5 risk haplotype and to identify interactions between the IBD5 and CARD15 loci. METHODS: A total of 1104 unrelated Caucasian subjects with inflammatory bowel disease (IBD) (496 CD, 512 UC, 96 indeterminate) and 750 ethnically matched controls were genotyped for three single nucleotide polymorphisms (SNPs) in the CD associated genes (OCTN1+1672, OCTN2-207, and IGR2230), and two flanking IBD5 tagging SNPs, IGR2096 and IGR3096. Data were analysed by logistic regression methods within STATA. RESULTS: OCTN variants were as strongly associated with UC and IBD overall as they were with CD (p = 0.0001; OR 1.3 (95% confidence interval 1.1-1.5)). OCTN variants were in tight linkage disequilibrium with the extended IBD5 risk haplotype D' 0.79 and 0.88, and r2 = 0.62 and 0.72 for IGR2096 and 3096, respectively. There was no deviation from a multiplicative model of interaction between CARD15 and IBD5 on the penetrance scale. CONCLUSIONS: The OCTN variants were associated with susceptibility to IBD overall. The effect was equally strong in UC and CD. Although OCTN variants may account for the increased risk of IBD associated with IBD5, a role for other candidate genes within this extended haplotype was not excluded. There was no statistical evidence of interaction between CARD15 and either OCTN or IBD5 variants in susceptibility to IBD.
Assuntos
Colite Ulcerativa/genética , Proteínas de Transporte de Cátions Orgânicos/genética , Adulto , Idade de Início , Cromossomos Humanos Par 5/genética , Doença de Crohn/genética , Feminino , Frequência do Gene , Marcadores Genéticos , Predisposição Genética para Doença , Genótipo , Humanos , Doenças Inflamatórias Intestinais/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Desequilíbrio de Ligação , Masculino , Proteína Adaptadora de Sinalização NOD2 , Polimorfismo de Nucleotídeo Único , Membro 5 da Família 22 de Carreadores de Soluto , SimportadoresRESUMO
Abdominal ultrasound examinations of 20 dogs with confirmed leptospirosis were reviewed retrospectively for renal abnormalities. Three dogs had a normal ultrasound examination. The remaining 17 dogs had sonographic abnormalities of the kidneys. These abnormalities, seen either alone or in combination, included renalmegaly (n=10), pyelectasia (n=9), increased cortical echogenicity (n=15), perinephric effusion (n=5), and a medullary band of increased echogenicity (n=6). At our institution, the medullary band of increased echogenicity has only been seen in dogs with leptospirosis and may therefore be a specific sonographic sign for this disease.
