PCR-based screening for the most prevalent alpha 1 antitrypsin deficiency mutations (PI S, Z, and Mmalton) in COPD patients from Eastern Tunisia

It is generally agreed that the protease inhibitor (PI) alleles PI S (Val264Glu) and PI Z (Lys342Glu) are the most common alpha 1 antitrypsin deficiency variants worldwide, but the PI Mmalton allele (ΔPhe52) prevails over these variants in some Mediterranean regions. In eastern Tunisia (Mahdia), we screened 100 subjects with chronic obstructive pulmonary disease for these variants. The PI S and PI Z alleles were genotyped by the previously described SexAI/Hpγ99I RFLP-PCR. We provide here a new method for PI Mmalton genotyping using mismatched RFLP-PCR. These methods are suitable for routine clinical application and can easily be reproduced by several laboratories, since they do not require extensive optimization, unlike the previously described bidirectional allele-specific amplification PCR for PI Mmalton genotyping. Our results were in agreement with previous reports from central Tunisia (Kairouan), suggesting that the PI Mmalton mutation is the most frequent alpha 1 antitrypsin deficiency-related mutation in Tunisia. \ua9 2013 Springer Science+Business Media New York

Correlation of EPHX1, GSTP1, GSTM1, and GSTT1 genetic polymorphisms with antioxidative stress markers in chronic obstructive pulmonary disease

This study was undertaken to ascertain if a relationship existed between oxidative status and polymorphisms of microsomal epoxide hydrolase X1 (EPHX1), glutathione S-transferase P1 (GSTP1), GSTM1, and GSTT1 in chronic obstructive pulmonary disease (COPD). Erythrocyte glutathione peroxidase (GSH-px), glutathione reductase (GR), superoxide dismutase (SOD), catalase (CAT), and plasma GST activities and total antioxidant status (TAS) as antioxidative stress markers were determined and compared either with individual and combined genotypes of EPHX1 exon 3, GSTP1 exon 5, GSTM1, and GSTT1 polymorphisms in COPD patients and healthy controls from the central area of Tunisia. Statistical data processing revealed significantly lower GSH-px, GR, SOD, CAT, GST, and TAS values in COPD patients in comparison to the control group (P <.001). As for genotypes, there was a no significant association in each of the 6 parameters and individual genotypes (P >.05). A significant correlation between the studied parameters and combined null GSTM1/null GSTT1 (GSH-px: P <.001, GR: P =.026, CAT: P =.018, GST: P =.022, TAS: P =.046), His113His EPHX1/null GSTM1 (GSH-px: P =.001, GST: P =.0012, TAS: P =.013), His113His EPHX1/Val105Val GSTP1 (GSH-px: P =.048, CAT: P =.026, GST: P =.031), and null GSTM1/Val105Val GSTP1 (GSH-px: P =.011, GR: P =.0028, GST: P =.0054, TAS: P =.032) was found in patients. In conclusion, combined genetic polymorphisms of GSTM1, GSTT1, GSTP1, and EPHX1 may have favorable effects on redox balance in COPD patients. \ua9 2011 Informa Healthcare USA, Inc