RESUMO
BACKGROUND & OBJECTIVES: Chronic obstructive pulmonary disease (COPD) is a complex chronic inflammatory disease of the respiratory system affecting primarily distal respiratory pathways and lung parenchyma. This study was aimed at investigating the association of COPD with IREB2, CHRNA5, CHRNA3, FAM13A and hedgehog interacting protein (HHIP) genes in a Tatar population from Russia. METHODS: Six single nucleotide polymorphisms (SNPs) (rs13180, rs16969968, rs1051730, rs6495309, rs7671167, rs13118928) were genotyped by the real-time polymerase chain reaction in this study (511 COPD patients and 508 controls). Logistic regression was used to detect the association of SNPs and haplotypes of linked loci in different models. Linear regression analyses were performed to estimate the relationship between SNPs and lung function parameters and pack-years. RESULTS: The rs13180 (IREB2), rs16969968 (CHRNA5) and rs1051730 (CHRNA3) were significantly associated with COPD in additive model [Padj =0.00001, odds ratio (OR)=0.64; Padj =0.0001, OR=1.41 and Padj =0.0001, OR=1.47]. The C-G haplotype by rs13180 and rs1051730 was a protective factor for COPD in our population (Padj =0.0005, OR=0.61). These results were confirmed only in smokers. The rs16969968 and rs1051730 were associated with decrease of forced expiratory volume in 1 sec % predicted (Padj =0.005 and Padj =0.0019). INTERPRETATION & CONCLUSIONS: Our study showed the association of rs13180, rs16969968 and rs1051730 with COPD and lung function in Tatar population from Russia. Further studies need to be done in other ethnic populations.
Assuntos
Proteína 2 Reguladora do Ferro/genética , Proteínas do Tecido Nervoso/genética , Doença Pulmonar Obstrutiva Crônica/genética , Receptores Nicotínicos/genética , Idoso , Proteínas de Transporte/genética , Etnicidade/genética , Feminino , Proteínas Ativadoras de GTPase/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Haplótipos , Humanos , Masculino , Glicoproteínas de Membrana/genética , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Doença Pulmonar Obstrutiva Crônica/patologia , Federação RussaRESUMO
We investigated the association of matrix metalloproteinases, the disintegrin and metalloprotease 33 and the tissue and serum inhibitors of proteinase gene polymorphisms with severe chronic respiratory diseases in Tatar children. We analyzed the case-control data sample from a total of 592 Tatar individuals, consisting of 119 children with chronic bronchitis, 138 with recurrent pneumonia and 335 control children residing in Ufa (Russia). The percentage of heterozygous genotype for the MMP9 (2660A>G) was higher among healthy children (52.54% vs 36.13% in chronic bronchitis patients, P(adj)=0.0033, P(cor)=0.033, odds ratio (OR)=0.51; and 36.96% in recurrent pneumonia group, P(adj)=0.0034, P(cor)=0.034, OR=0.53). The MMP12 (-82A>G) locus was associated with chronic bronchitis in the additive model (P(adj)=0.0091, P(cor)=0.09, OR=0.45, ß=-0.798). The relationship between the 6A6A genotype of MMP3 (-1171 5A>6A) (P(adj)=0.0013, P(cor)=0.013, OR=3.91) and the 6A-A haplotype of MMP3 (-1171 5A>6A) and MMP12 (-82A>G) and recurrent pneumonia were unraveled (Padj=0.001, P(cor)=0.01, OR=2.07). This haplotype was also associated with a higher risk of chronic bronchitis (P(adj)=0.0012, P(cor)=0.012, OR=2.15). The TIMP3 (-1296T>C) was associated with recurrent pneumonia in the dominant model (P(adj)=0.0031, P(cor)=0.031, OR=1.91). The MMP9, MMP3 and TIMP3 (tissue inhibitors of matrix metalloproteinases) polymorphisms and MMP3 and MMP12 haplotypes may play a substantial role in susceptibility to severe airway and lung injury in children with chronic bronchitis and recurrent pneumonia.
