Frequency of alpha-1 antitrypsin deficiency and unexpected results in COPD patients in Turkey; rare variants are common

Authors: MUSTAFA ÇÖRTÜK, BARIŞ DEMİRKOL, MELİH AKAY ARSLAN, UMUT İLHAN, YUNUS EMRE KALKAN, DEMET TURAN, ŞULE GÜL, HALİT ÇINARKA, KÜRŞAD NURİ BAYDİLİ, ERDOĞAN ÇETİNKAYA

Abstract: Background/aim: Alpha-1 antitrypsin (?1-AT) is a protease inhibitor that is largely released from liver cells. It inhibits neutrophil elastase and its deficiency increases the risk of developing chronic obstructive pulmonary disease (COPD). The frequency of ?1-AT deficiency has been reported with different prevalence rates in different parts of the world. The most common ?1-AT variant causing ?1-AT deficiency is the Pi*Z allele. In this study, we aimed to determine the frequency of the ?1-AT genotypic variant in COPD patients in our country. Materials and methods: In this study, 196 consecutive COPD patients admitted to our clinic were included. In addition to recording the demographic data of the volunteers, a dry drop of blood sample was taken from the fingertip for the SERPINA1 genotype study. Results: One hundred and fifty-eight (80.6%) of the patients were male and the mean age was 56.92 ± 9.84 years. A variant in the SERPINA1 gene was detected in a total of 14 (7.1%) COPD patients. Pi*ZZ homozygous variant was detected in only 1 (0.51%) patient, while Pi*MZ was detected in 3 (1.53%) patients. The Pi*S variant was never detected. Various rare heterozygous variants were detected in 9 (4.6%) patients and a single point mutation was found in one (0.51%) patient. Serum ?1-AT levels were significantly lower in patients with variants compared to the Pi*MM group (p < 0.001). Conclusion: In this study, which investigated the genotypic ?1-AT variant frequency in COPD patients for the first time in our country, we found that the percentage of homozygous Pi*ZZ patients was 0.51%, but when heterozygous ?1-AT gene variant and single point mutation were included, the frequency was 7.1%. At the same time, while the Pi*S variant was never detected, rare variants were found more frequently than expected.

Keywords: Alpha 1-antitrypsin deficiency, chronic obstructive pulmonary disease, screening, mutation, genome, gene frequency

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