Heterozygous Genotype rs17580 AT (PiS) in SERPINA1 is Associated with COPD Secondary to Biomass-Burning and Tobacco Smoking: A Case-Control and Populational Study

Int J Chron Obstruct Pulmon Dis. 2020 May 27:15:1181-1190. doi: 10.2147/COPD.S247446. eCollection 2020.

Abstract

Purpose: The protease inhibitor S (PiS) and Z (PiZ) variants have been stated as the only genetic cause of chronic obstructive pulmonary disease (COPD) in Caucasians. However, its frequency in admixed populations is low. We aimed to identify genetic susceptibility between PiS (rs17580) and PiZ (rs28929474) polymorphisms with COPD related to tobacco smoking and biomass-burning smoke as well as to determine its frequencies in Mestizo and Amerindian populations from Mexico.

Patients and methods: One thousand and eight hundred seventy-eight subjects were included in two comparisons of cases and controls, (1) smokers with and without COPD (COPD-S, n=399; SWOC, n=1106); (2) Biomass-burning smoke-exposed subjects with and without COPD (COPD-BS, n=98; BBES, n=275). In addition, 2354 Mexican subjects identified as Mestizos (n=1952) and Amerindian (n=402) were included. The population structure was evaluated using 59 informative ancestry markers.

Results: The AT genotype of rs17580 is associated with COPD in both comparisons (COPD-S vs SWOC p<0.001, OR=2.16; COPD-BS vs BBES p<0.0001, OR=11.50). The population of the Mexico-North has a greater Caucasian contribution (54.7%) compared to the center (46.9%) and southeast (42.7%).

Conclusion: The rs17580, AT genotype, is associated with COPD in Mexican-Mestizo smokers and exposed to biomass-burning smoke. The rs17580 AT is more frequent in the Mexican-Mestizo population of the North of the country, which has a high Caucasian component.

Keywords: A1AT; AAT; COPD; PiS; PiZ; SERPINA1; biomass-burning smoke; tobacco smoking.

MeSH terms

  • Biomass
  • Case-Control Studies
  • Genotype
  • Humans
  • Mexico / epidemiology
  • Pulmonary Disease, Chronic Obstructive* / diagnosis
  • Pulmonary Disease, Chronic Obstructive* / epidemiology
  • Pulmonary Disease, Chronic Obstructive* / genetics
  • Tobacco Smoking
  • alpha 1-Antitrypsin* / genetics

Substances

  • SERPINA1 protein, human
  • alpha 1-Antitrypsin

Grants and funding

This work was supported by the allocated budget to research (R.F.V.-HLA Laboratory) from the Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas (INER) and partially supported by the resource assigned to INER, 555 managed in Legislatures of the Chamber of Deputies through its Committee on Equality and Gender for the budgetary allocation for the Care of Using Wood Associated Diseases. Funded by PAPIIT-UNAM IA303917 (A.I.J.-M Centro de Estudios Antropológicos- Facultad de Ciencias Políticas 560 y Sociales, UNAM).