No abstract

Background: Atopic dermatitis (AD) is a chronic multifactorial allergic disease with unclear etiology. The antimicrobial human β-defensin 1 is chemotactic for dendritic cells, which are important regulators of allergic immune responses. In an attempt to identify useful markers that could predict susceptibility to AD, we investigated single nucleotide polymorphisms (SNPs) of the β-defensin 1 gene (DEFB1) with potential functional consequences. Methods: Four SNPs of the DEFB1 gene were genotyped either by real-time polymerase chain reaction or polymerase chain reaction-restriction fragment length polymorphisms in 59 patients with AD and 151 controls from the Mexican population. Correlation analyses were carried out between genetic, environmental and clinical variables in AD patients. Results: The genotypes associated with susceptibility to AD and no other allergy were 692 GG (OR = 3.21, 95% CI 1.37–7.34) and 1654 AA (OR = 17.37, 95% CI 1.62–860.83). The allele 668 C is a risk factor for AD (OR = 2.23, 95% CI 1.22–4.01) and the allele A in site 1836 correlates with earlier age at onset (Spearman’s ρ = 0.232; p = 0.03). The prolonged duration of breastfeeding correlates with earlier age at onset as well as with the severity of AD. Conclusions: The DEFB1 gene is probably involved in the incidence and development of AD, but additional functional studies will be necessary to understand the biological role of these SNPs.

We describe for the first time the high-resolution profiling of HLA-A, -B, -C, -DRB1, -DQB1 and -DPB1 in a culturally and geographically distinct Mexican ethnic group, the Tarahumaras. The alleles most frequently found by reference strand-mediated conformational analysis in this population were for class I: HLA-A*240201, *020101/09, *0206, *310102, *680102; HLA-B*4002, *1501, *510201, *3501/02/03, *4005, *4801; HLA-Cw*0304, *0801, *0102, *040101; and for class II: HLA-DRB1*080201, *1402, *040701; HLA-DQB1*0402, *0301, *0302/07; HLA-DPB1*0402, *0401, *020102. In addition, a novel allele, HLA-A*0257, was found. Based on comparison of presently known HLA-DRB1 and -DQB1 allele frequencies in Amerindian groups and worldwide populations, the Tarahumaras are unexpectedly more related to the geographically and linguistically distant Aymara and Terena Amerindian groups than they are to neighbouring tribes.

Rheumatoid arthritis (RA) is the prototype of the rheumatic diseases worldwide. Methotrexate (MTX) is the drug of first choice in the treatment of this disease due to its immunosuppressant effect. However, side events are present in 30% of the patients. The C677T and A1298C polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) gene are involved in the metabolism of MTX. Earlier studies reported an association between these polymorphisms and elevation of hepatic enzymes. We analyzed the frequencies of both polymorphisms and the presence of transaminasemia in 70 Mexican patients with rheumatic arthritis treated with MTX. The 19% (13/70) of patients had an increase in the serum level of transaminases. The A1298C polymorphism was associated with elevation of transaminases (P ¼ 0.024). The identification of MTHFR genotypes for C677T and A1298C polymorphisms could lead clinicians to identify patients in risk of elevation of transaminases, and give them an individualized treatment, as is a goal of pharmacogenetics.