Although it has been reported that some of the genes involved in inflammation are associated with pulmonary and infectious diseases [16, 17, 21, 25–28], to date, no direct association between these polymorphisms and infection by influenza A/H1N1 virus has been reported. In the present study, the logistic regression analysis of cases and controls showed that TNF rs361525 (AA), rs1800750 (AA), and LTA rs909253 (AG) were associated with high risk of infection by pandemic influenza A/H1N1. Although mortality of the A/H1N1 patients was greater than that of the ILI patients (p <0.001), only genotype AG of LTA rs909253 demonstrated an association with mortality (p = 0.06) just missing being statistically significant. This finding may indicate that being a carrier of genotype AG LTA at rs909253 entails a poorer prognosis for this illness.
Some biomarkers, such as CRP, LDH, leukopenia, and hypoxemia [7, 8] have been considered as predictors for severe illness by influenza A/H1N1 virus. In this study, we found that elevated values of laboratory test parameters (BUN, CPK, and leukocyte titer) were associated with TNF (rs1800629 AG, rs1800750 AA), and IL1B (genotype AA). These results may indicate that being a carrier of these polymorphisms in particular may be associated with severer organic damage by infection by influenza A/H1N1 virus. However, in the case of IL8, the homozygous AA appeared to offer a certain degree of protection against severe illness; this may be explained, in part, by the association of a higher concentration of oxygen in the blood (PaO2 >60 mm Hg) with this genotype.
Although susceptibility for presenting an adverse clinical course (i.e., sepsis, septic shock, multiples organ failure, or death) varies due to different degrees of inflammatory response , genetic factors of the host may influence the nature and intensity of this response. The present study is the first to demonstrate that the polymorphisms in genes related to the inflammatory response may, in some manner, be influencing the risk of infection by influenza A/H1N1 virus and of death from this illness. One possible mechanism may be the formation of disequilibria in the bond between alleles, creating haplotypes that differentially affect the expression and activity of cytokines and chemokines, thereby resulting in a severer clinical course for the infection.
To avoid variability in our results, we studied a homogeneous population of Mexican mestizos. Although the sampling size was a limitation in our study, we were able to demonstrate statistically significant differences in the distribution of genotypes in terms of infection, mortality, and biomarkers between cases and controls, thus suggesting a strong association with the illness. However, infection by influenza A/H1N1 virus is a very complex illness that involves not only the association of environmental factors and the genetic make-up and biology of the individual per se, but also the presence of co-morbidities that may contribute to a greater severity of the illness [4, 5].
We had limitations. For example, contacts exhibited significant titers of specific anti-A/H1N1 antibodies, supporting the fact that they were in contact with the A/H1N1 virus. Additionally is necessary clear that is not a patients group, we just include unrelated contacts in this study (e.g. family in law persons, home workers, etc.). They were in close contact with patients when the latter exhibited acute respiratory illness. None of these household contacts developed respiratory illness. However, the presence of antibody would not confirm infection with A/H1N1 virus because there is the likelihood of cross-reactivity . But, when a person with positivity of antibodies that had contact with an A/H1N1 virus infected patient, the infection cannot be excluded . The gold standard for identifying the infection to A/H1N1 virus is real time PCR test; however to identify the presence of the virus in symptomatic patients is necessary that the patients be assessed during the first days from the beginning of the disease, the probability of identifying the virus by molecular test in asymptomatic patients is very low and not practical .
With the high mortality rate from the 2009 influenza A/H1N1 pandemic in Mexico , the approach used in this work could acquire great importance, as the study of polymorphisms may be useful in predicting the conduct that the infection would follow during future outbreaks of influenza A/H1N1 in Mexico.