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Alpha-1-antitrypsin (protease inhibitor) phenotypes and longevity
1Department of Clinical Biochemistry, Royal Prince Alfred Hospital, Camperdown, NSW, Australia.
Abstract:
We have tested the hypothesis that the protease inhibitor phenotypes MZ and MS are disadvantageous and reduce survival by comparing the prevalence of these phenotypes in a group of 707 very old people (hospital patients) with the prevalences reported in younger populations of blood donors. The MS and MZ phenotypes appear to be no less common among those who have survived to old age, but a highly significant difference was found in the occurrence of the M subtypes. The M1 type was more common in the elderly, and the M heterozygotes were less common than would be predicted from the reported incidence in younger groups and from the Hardy-Weinberg equilibrium. This discrepancy appeared to be smaller in subjects of Mediterranean origin than in those of British or Irish genetic background.
Insights
Protease inhibitor phenotypes MZ and MS do not appear disadvantageous for survival into old age. However, M1 subtypes were more common in the elderly, suggesting altered M subtype frequencies with age.
Area of Science:
- Genetics
- Human Longevity
- Biochemistry
Background:
- Protease inhibitor (PI) phenotypes, including MZ and MS, are studied for their potential impact on health and survival.
- Previous research suggests certain PI phenotypes might be disadvantageous, but evidence regarding long-term survival is limited.
Purpose of the Study:
- To investigate whether protease inhibitor (PI) phenotypes MZ and MS are disadvantageous, affecting survival to old age.
- To compare the prevalence of these PI phenotypes in a cohort of very old individuals with data from younger populations.
Main Methods:
- A comparative study involving 707 elderly hospital patients.
- Prevalence data of PI phenotypes (MZ, MS, and M subtypes) were collected and compared with reported incidences in younger blood donor populations.
- Analysis included Hardy-Weinberg equilibrium calculations to assess genetic distribution.
Main Results:
- The prevalence of MS and MZ phenotypes was similar in the elderly cohort and younger populations, indicating they are not disadvantageous for survival.
- A significant difference was observed in the occurrence of M subtypes, with M1 being more common in the elderly.
- M heterozygotes were less common in the elderly than predicted, with this discrepancy being smaller in individuals of Mediterranean origin compared to those of British or Irish background.
Conclusions:
- Protease inhibitor (PI) phenotypes MZ and MS do not appear to confer a survival disadvantage into old age.
- Age-related shifts in M subtype frequencies, particularly an increase in M1, are suggested.
- Genetic background may influence the observed discrepancies in PI subtype prevalence with age, with Mediterranean populations showing a smaller effect.