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Oak Ridge Conference |
1
Max McGee National Research Center for Juvenile Diabetes, The Medical College of Wisconsin, 8701 Watertown Plank Rd., Milwaukee, WI 53226.
2
Diagnostic Laboratories, Blood Center of Southeastern Wisconsin, Milwaukee, WI 53201.
3
Third Wave Technologies Inc., Madison, WI 53719.
aAuthor for correspondence. Fax 414-456-6663; e-mail mhessner{at}mcw.edu.
Abstract
Background: 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.
Methods: The frequencies of factor V G1691A Leiden (FVL), factor II (FII) G20210A, methylenetetrahydrofolate reductase (MTHFR) C677T, glycoprotein Ia (GPIa) C807T, glycoprotein IIIa (PlA1/PlA2) 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: 1739 years (n = 979; 505 males and 474 females), 4059 years (n = 900; 526 males and 374 females), and 6085 years (n = 810; 530 males and 280 females).
Results: The PlA2 allele frequency decreased from 17.5% to 15.7% and 14.1% in the 1739 years, 4059 years, and 6085 years age groups, respectively (n = 5094 alleles; P = 0.025). Among ACE DD males, the PlA2 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.
Conclusions: These data suggest that PlA2 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 PlA2 allele, as well as the ACE DD/PlA2 allelic combination, on overall health and longevity.
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