Age-dependent Prevalence of Vascular Disease-associated Polymorphisms among 2689 Volunteer Blood Donors

• Published in: Clinical chemistry (Baltimore, Md.) Vol. 47; no. 10; pp. 1879 - 1884
• Main Authors: Hessner, Martin J, Dinauer, David M, Kwiatkowski, Robert, Neri, Bruce, Raife, Thomas J
• Format: Journal Article
• Language: English
• Published: Washington, DC Am Assoc Clin Chem 01.10.2001; American Association for Clinical Chemistry
• Subjects: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Antigens, CD - genetics; Biological and medical sciences; Blood Donors; Cardiology. Vascular system; Cardiovascular system; Cohort Studies; Coronary heart disease; European Continental Ancestry Group - genetics; Factor V - genetics; Female; Heart; Humans; Integrin alpha2; Integrin beta3; Investigative techniques, diagnostic techniques (general aspects); Male; Medical sciences; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Mutation; Oxidoreductases Acting on CH-NH Group Donors - genetics; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Peptidyl-Dipeptidase A - genetics; Platelet Membrane Glycoproteins - genetics; Polymorphism, Genetic; Prevalence; Prothrombin - genetics; Vascular Diseases - genetics; Human; Enzyme; Volunteer; Age criterion; Cardiovascular disease; Glycoprotein IIIa; Genetic determinism; Epidemiology; Peptidases; Hemostasis; Peptidyl-dipeptidase A; Blood donation; Cohort study; Hydrolases; Peptidyl-dipeptidases; Polymorphism
• ISSN: 0009-9147; 1530-8561
• DOI: 10.1093/clinchem/47.10.1879

The development of vascular disease involves the interaction of genetic and environmental factors. Because vascular disease is a major contributor to mortality in Western societies, we hypothesized that deleterious polymorphisms associated with hemostasis decrease in frequency among a healthy population as a function of age. The frequencies of factor V G1691A Leiden (FVL), factor II (FII) G20210A, methylenetetrahydrofolate reductase (MTHFR) C677T, glycoprotein Ia (GPIa) C807T, glycoprotein IIIa (Pl(A1)/Pl(A2)) T1565C, and angiotensin-converting enzyme (ACE) intron 16 insertion/deletion (I/D) alleles were determined among 2689 healthy Caucasian whole-blood donors. For analysis, participants were divided into three age groups: 17-39 years (n = 979; 505 males and 474 females), 40-59 years (n = 900; 526 males and 374 females), and 60-85 years (n = 810; 530 males and 280 females). The Pl(A2) allele frequency decreased from 17.5% to 15.7% and 14.1% in the 17-39 years, 40-59 years, and 60-85 years age groups, respectively (n = 5094 alleles; P = 0.025). Among ACE DD males, the Pl(A2) allele frequency decreased from 20.8% to 16.1% and 9.1% in the same groups, respectively (n = 810 alleles; P = 0.001). No statistically significant decrease in genotype or allele frequency was observed among carriers of FVL, FII 20210A, MTHFR 677T, GPIa 807T, or ACE D. These data suggest that Pl(A2) carriers, especially those who are ACE DD, are statistically less prevalent among older healthy blood donors compared with their younger counterparts. These observations suggest an important, deleterious, time-dependent impact of the Pl(A2) allele, as well as the ACE DD/Pl(A2) allelic combination, on overall health and longevity.