Point Mutation May Help Explain Different National COVID-19 Death Rates

By Will Boggs MD

October 02, 2020

NEW YORK (Reuters Health) - Ethnic differences in the frequencies of alpha-1 antitrypsin deficiency alleles might contribute to national differences in COVID-19 fatality rates, researchers report.

"It was interesting to see how one point mutation in a relevant gene can tell the difference on a national level between high and low mortality rates," Dr. Noam Shomron of Tel Aviv University, in Israel, told Reuters Health by email.

Two single nucleotide polymorphisms (SNPs) in SERPINA1, which encodes alpha-1 antitrypsin, are responsible for antitrypsin deficiency in humans. The PiZ allele is associated with greater deficiency than the PiS allele. Earlier studies have identified higher COVID-19 infection rates among carriers than among non-carriers of PiZ.

Dr. Shomron and colleagues examined the possible association between the distributions of these SNPs and COVID-19 epidemiology across different regions of the world.

The PiZ allele was considerably less frequent in East and Southeast Asian populations (two alleles per 1,000 individuals) than in South European populations (17 alleles per 1,000 individuals). And the PiS allele showed even greater disparity, with five alleles versus 86 per 1,000, respectively, the researchers report in the FASEB Journal.

Covariance analysis revealed a significant positive association between estimated national alpha-1 antitrypsin deficiency (based on allele frequencies) and COVID-19 mortality rates after controlling for Human Development Index, urbanization level, volume of international travel, and proportions of elderly people.

Combined data from 67 countries also showed a significant direct correlation (Pearson R=0.54) between alpha-1 antitrypsin deficiency rates and COVID-19 fatalities.

"If proved true, these mutations could be used to screen the population and rank those at high risk for lung complications once infected with COVID-19," Dr. Shomron said. "This also means that it could be used to prioritize who will get the vaccination first, once one is available."

Coauthor Dr. David Gurwitz, also at Tel Aviv University, told Reuters Health by email, "Of course, the population screening we offer in our article requires validation of our hypothesis. A key purpose for publishing this as a hypothesis was to get attention of clinicians in corona wards globally."

He added, "Several studies from the USA and the UK indicate that African and Asian minorities are at higher risk of severe COVID-19 compared with Europeans, which seems to negate our hypothesis. However, one should keep in mind that in these countries, individuals of African and Asian descent are more likely to come from lower socioeconomic status compared with Europeans, and are less likely to have good healthcare access."

SOURCE: https://bit.ly/2ELwBYM The FASEB Journal, online September 22, 2020.