Age-dependent prevalence of vascular disease-associated polymorphisms among 2689 volunteer blood donors

Background: The development of vascular disease involves the interaction of genetic and environmental factors. Because vascular disease is a major con tributor to mortality in Western societies, we hypothesized that deleteriou s polymorphisms associated with hemostasis decrease in frequency among a he althy population as a function of age. Methods: The frequencies of factor V G1691A Leiden (FVL), factor II (FII) G 20210A, methylenetetrahydrofolate reductase (MTHFR) C677T, glycoprotein Ia (GPIa) C807T, glycoprotein IIIa (pl(A1)/pl(A2)) T1565C, and angiotensin-con verting enzyme (ACE) intron 16 insertion/ deletion (I/D) alleles were deter mined among 2689 healthy Caucasian whole-blood donors. For analysis, partic ipants 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). Results: 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 DID males, the pl(A2) allele freq uency decreased from 20.8% to 16.1% and 9.1% in the same groups, respective ly (n = 810 alleles; P = 0.001). No statistically significant decrease in g enotype or allele frequency was observed among carriers of FVL, FII 20210A, MTHFR 677T, GPIa 807T, or ACE D. Conclusions: These data suggest that pl(A2) carriers, especially those who are ACE DD, are statistically less prevalent among older healthy blood dono rs 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. (C) 2001 American Association for Clinical Chemistry.