1. INTRODUCTION
Alpha-1-antitrypsin (A1AT) belongs to the serpine protease inhibitor
(serpin) family, as are alpha-1-antichymotrypsin, C1 inhibitor,
antithrombin, and neuroserpine. It is known as alpha-1-antiproteinase
and is also encoded as a proteinase inhibitor (PI).1A1AT is synthesized by hepatocytes, macrophages, intestinal epithelial
cells, and bronchial epithelial cells.2,3 With a
plasma half-life of five days, A1AT is found in all body fluids and most
tissues. A1AT is an acute-phase protein and one of the potent regulators
of neutrophil activation, acting through protease inhibition and other
mechanisms.4 On the other hand, A1AT is the strongest
inhibitor of bacterial serine proteases, proteinase 3, and neutrophil
elastase.4,5
The A1AT gene consists of two alleles. Most of the genotype distribution
in the human population are combinations of the M, S, and Z alleles.
Furthermore, the PI*MM genotype is considered normal, which is
encountered in 85-95% of the world population and can synthesize 100%
normal A1AT.6 On the other hand, the genotype
distributions of PI*MS, PI*SS, PI*MZ, PI*SZ, and PI*ZZ alleles are
5-15% worldwide. These alleles can achieve 80%, 60%, 55%, 40%, and
15% normal A1AT synthesis, respectively.7
Most of the mutations in the A1AT gene result in mutant protein
synthesis that lacks function and damages the cell where it
accumulates.8 The PI*ZZ genotype carries a high risk
of diseases associated with A1AT insufficiency, while the PI*SZ, PI*SS,
and PI*MZ genotypes are only potentially risky.9,10Especially the PI*SZ allele causes pulmonary emphysema in
smokers.7
The SARS-CoV-2 virus (COVID-19) was identified as a result of research
conducted on a group of patients with acute respiratory symptoms in the
form of fever, cough, and shortness of breath in Wuhan Province, China,
in late 2019.11 Approximately 81% of symptomatic
patients infected with COVID-19 show mild, 14% severe, and 5% critical
disease course.12
A study covering 97 countries with a total sample of 5.264 million
projected that there are 190 million carriers of a risky allele in the
A1AT.10 Of these alleles 142 million (74.8%) are
PI*MS, 42 million (22.3%) are PI*MZ, 4 million (2.1%) are PI*SS, 1.269
million (0.7%) are PI*SZ, 181,000 (0.1%) are PI*ZZ
genotype.10
We hypothesized that the geographic distributions of COVID-19 prevalence
and risky A1AT allele prevalence are similar. Therefore, we aimed to
investigate whether there is a relationship between the geographical
density of the COVID-19 pandemic and the distributions of risky A1AT
alleles.