Genetic factors associated with the absence of atherosclerosis in octogenarians.
BACKGROUND
Atherosclerosis (ATS) is a common age-related disease of large arteries. The prevalence of older subjects with vascular successful aging (VaSA), defined as the absence of clinical symptoms and instrumental signs of ATS, is low in Western countries. The possible contribution of genetics to the VaSA phenomenon is not known.


METHODS
We investigated the distribution of four genetic polymorphisms (angiotensin converting enzyme [ACE], methylenetetrahydrofolate reductase [MTHFR], apolipoprotein E [apo E], and paraoxonase [PON] genes) in 30 subjects with VaSA, 30 subjects with moderate carotid atherosclerosis (ATS group), and 161 controls with a negative history for cardiovascular disease. Clinical examination; ultrasonographic examination of carotid, vertebral, abdominal aortic, iliac, and femoral arteries; and electrocardiogram were performed.


RESULTS
The frequency of PON 192 B allele was lower in VaSA patients (13%) compared with ATS patients (37%) and controls (46%) ( p =.06 and.006, respectively); B/B homozygotes were 27% in the ATS group, 12% in controls, and 0% in the VaSA group. The frequency of the MTHFR thermolable + allele was higher in VaSA (0.51) compared with ATS (0.39) and controls (0.40) (VaSA vs C, p =.006). No differences in the distribution of ACE I/D and apo E alleles emerged between the three groups.


CONCLUSIONS
The low prevalence of the PON 192 B allele in the VaSA subjects suggests that this polymorphism might have an important role in VaSA, probably by hydrolyzing lipid peroxides and thus preventing low-density lipoprotein from undergoing the oxidative modification. This finding further supports the oxidative hypothesis of ATS.
Department of Clinical and Experimental Medicine, Section of Internal Medicine II. Vascular Surgery, University of Ferrara, Italy.
Giovanni
G
Zuliani
Antonio
A
Cherubini
Stefano
S
Volpato
Elisabetta
E
Palmieri
Patrizia
P
Mecocci
Paola
P
De Rango
Piergiorgio
P
Cao
Fabrizio
F
Costantini
Andrea
A
Mezzetti
Francesco
F
Mascoli
Umberto
U
Senin
Renato
R
Fellin
D000368:Aged; D000369:Aged, 80 and over; D001057:Apolipoproteins E / Q000235:genetics; D001161:Arteriosclerosis / Q000235:genetics*; D043303:Aryldialkylphosphatase; D004950:Esterases / Q000235:genetics; D005260:Female; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D011110:Polymorphism, Genetic
D001057:Apolipoproteins E; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D004950:Esterases; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human; D007703:Peptidyl-Dipeptidase A