Combined analysis of EPHX1, GSTP1, GSTM1 and GSTT1 gene polymorphisms in relation to chronic obstructive pulmonary disease risk and lung function impairment

Smoking is considered as the major causal factor of chronic obstructive pulmonary disease (COPD). Nevertheless, a minority of chronic heavy cigarette smokers develops COPD. This suggests important contribution of other factors such as genetic predisposing. Our objective was to investigate combined role of EPHX1, GSTP1, M1 and T1 gene polymorphisms in COPD risk, its phenotypes and lung function impairment. Prevalence of EPHX1, GSTP1, M1 and T1 gene polymorphisms were assessed in 234 COPD patients and 182 healthy controls from Tunisia. Genotypes of EPHX1 (Tyr113His; His139Arg) and GSTP1 (Ile105Val; Ala114Val) polymorphisms were performed by PCR-RFLP, while the deletion in GSTM1 and GSTT1 genes was determined using multiplex PCR. Analysis of combinations showed a significant association of 113His/His EPHX1/null-GSTM1 (OR=4.07) and null-GSTM1/105Val/Val GSTP1 (OR =3.56) genotypes with increased risk of COPD (respectively P=0.0094 and P=0.0153). The null-GSTM1/ null-GSTT1, 105Val/Val GSTP1/null GSTT1, 113His/His EPHX1/null-GSTM1 and null-GSTM1/105Val/Val GSTP1 genotypes were related to emphysema (respectively P=0.01; P=0.009; P=0.008 and P=0.001). Combination of 113His/His EPHX1/null-GSTM1 genotypes showed a significant association with the decrease of Δ FEV1 in patients (P =0.028).In conclusion, our results suggest combined EPHX1, GSTP1, GSTM1 and GSTT1 genetic polymorphisms may play a significant role in the development of COPD, emphysema and decline of the lung function.     

Clinical and molecular characteristics of the 2009 pandemic influenza H1N1 infection with severe or fatal disease from 2009 to 2011 in Shenzhen,China

In the past 3 years, the 2009 pandemic influenza virus H1N1 (pH1N1) has led to many severe or fatal cases. The virus‐related factors that cause severe or fatal disease are not clear. The clinical and molecular characteristics of pH1N1 infections with severe or fatal disease were examined to understand the correlation between pH1N1 infection and disease severity. Since 2009, three pH1N1 influenza epidemic outbreaks have occurred in Shenzhen, China. One hundred forty‐six severe cases were confirmed in the first wave in 2009. In severe cases, a high proportion (49.3%) of patents displayed high fever (>39.0°C), and 73.2% of patients had pneumonia and tracheobronchitis. Seven fatal cases were recorded: three with viral encephalitis and four with respiratory failure. The results of sequencing and phylogenetic analysis showed that the viruses from fatal or severe cases were scattered throughout the phylogenetic tree. Four substitutions (D222G, D222N, D222E, and Q223R) were observed on the 220‐loop of the receptor‐binding sites of the HA gene. Both D222G and D222N were associated statistically with severe disease. The 2011 viruses had evolved into two distinct branches. Ten specific point mutations occurred in the 2011 virus. In summary, high fever, lower respiratory tract infections and serious complications were the main features of severe cases. Gene variation seemed not to be the main reason for severe disease. Vaccination is the effective mean to prevent infection and severe disease. J. Med. Virol. 85:405–412, 2013. © 2012 Wiley Periodicals, Inc.