PCR-Based Screening for the Most Prevalent Alpha 1 Antitrypsin Deficiency Mutations (PI S, Z, and Mmalton) in COPD Patients from Eastern Tunisia

• Published in: Biochemical genetics 2013-10, Vol.51 (9-10), p.677-685
• Main Authors: Denden, Sabri, Lakhdar, Ramzi, Boudawara Keskes, Nadia, Hamdaoui, Mohamed Hedi, Chibani, Jemni Ben, Khelil, Amel Haj
• Format: Article
• Language: English
• Subjects: Alleles; alpha 1-Antitrypsin - genetics; alpha 1-Antitrypsin Deficiency - diagnosis; alpha 1-Antitrypsin Deficiency - genetics; Biochemistry; Biomedical and Life Sciences; Biomedicine; Chronic obstructive pulmonary disease; Genetic Variation; genotyping; Genotyping Techniques; Human Genetics; Humans; Medical Microbiology; Mutation; new methods; patients; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Prevalence; Proteinase inhibitors; Pulmonary Disease, Chronic Obstructive - genetics; screening; Tunisia; Zoology
• ISSN: 0006-2928; 1573-4927
• DOI: 10.1007/s10528-013-9597-6

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.