Methods: Sixteen single nucleotide polymorphisms (SNPs) in TNF, IL6, IFNG, TGFB1, IL10, CD14, TLR4, TLR7, TLR8, FLG, ADRB2genes were genotyped in 311 family trios (n=944), by SSP-PCR or allelic-specific Taqman assay techniques. PLINK and Haploview softwares were used for data analysis.
Results: TDT analysis showed that, among the 16 SNPs studied, three SNPs were associated to susceptibility to the development of asthma, rs1800629 (TNF-308) minor A allele (p=0,0031; OR=0,5), rs1800795 (IL6-174) minor allele C (p=1,87exp-7; OR=0,35) and rs1800471 (TGFB1+915) minor allele C (p=1,34exp-8; OR=0,11) were significantly less frequently transmitted within the families, suggesting a protective effect of these alleles against the development of asthma. After ethnicity stratification, the same SNPs showed significant association in White patients (n=168), but not in Mullato patients (n=154) for TNF-308A, which is possibly related to number of patients analyzed in this population. IL6-174, TNF-308 and TGFB1+915 haplotype association analysis showed risk to asthma (GGG, OR=5,3, p=1E-5) and protection to asthma (CGC, OR=0,24, p=1,9E-4).
Conclusions: Our results revealed a protective association of TNF-308A, IL6-174C e TGFB1+915C variants in a Brazilian family-based association study confirming previously reported data and established two new haplotypes conferring asthma susceptibility.