Tumor necrosis factor alpha promoter polymorphisms in Mexican patients with dengue fever.

Increased levels of tumor necrosis factor alpha (TNF-α) in patients with dengue have been reported. Various polymorphisms have been identified in the promoter region of the TNF-α gene that may affect its transcription. The purpose of the present study was to evaluate the relationship between polymorphisms of TNF-α gene and the genetic susceptibility to dengue fever in a group of patients from Morelos State, Mexico. The TNF-α polymorphisms (positions -238 and -308) were determined by PCR-RFLP technique in 130 patients with dengue (85 with dengue fever and 45 with dengue hemorrhagic fever) and 169 healthy controls. The patients were selected from cases reported in Morelos State from 1997 to 2003. The whole group of dengue patients showed a decreased frequency of TNF-α -238 A allele when compared to healthy controls (p = 0.01, OR = 0.19, 95%CI = 0.02-0.78). When the analysis was made separately in dengue fever and dengue hemorrhagic fever patients, the decreased frequency of TNF-α -238 A allele only remained significant in patients with DHF when compared to healthy controls (p = 0.034). This work suggests a possible association of TNF-α -238 A allele with protection to develop symptomatic disease.

HLA class I and II polymorphisms in Mexican Mestizo patients with dengue fever.

Host genetics in dengue hemorrhagic fever (DHF) pathophysiology has not been extensively investigated. Most studies have focused on HLA in different populations; however these reported associations have not been replicated. We performed a case-control study to analyze possible associations of HLA-A, HLA-B, HLA-Cw, HLA-DRB1 and HLA-DQB1 alleles with clinical disease severity caused by dengue virus infection. Our population consisted of 39 individuals (DF: 23, DHF: 16) and 34 healthy controls from the State of Morelos, Mexico. HLA loci were genotyped by nucleotide sequencing method. Statistical analyses revealed associations in three alleles: HLA-B*35 was negatively associated with symptomatic disease (p<1x10(-4), p(c)=0.01, OR=0.12, 95%CI=0.037-0.39), and DF (p=0.0007, p(c)=0.03, OR=0.13, 95%CI=0.031-0.51). HLA-DQB1*0302 was positively associated with DHF (p=0.018, p(c)=NS, OR=5.02, 95%CI=1.05-25.34), and negatively with DF (p=0.011, p(c)=NS, OR=0.23, 95%CI=0.06-0.84). HLA-DQB1*0202 was positively associated with DF only (p=0.012, p(c)=NS, OR=7.0, 95%CI=1.11-73.8). We identified possible associations of HLA-B and HLA-DQB1 alleles with the risk of developing symptomatic disease, DF and DHF in a Mexican Mestizo population.