Abstract 9300: Gene Polymorphisms In Il-10 And Inf-γ are Associated With Early Atherosclerosis In Coronary but not in Carotid Arteries: A Study Of 122 Autopsy Cases of Young Adults

Atherosclerosis is a complex disease that involves both genetic and environmental factors. However, the influence of genetic variations to its early development remains unclear. We examined the association of single-nucleotide polymorphisms (SNPs) with atherosclerotic severity in the anterior descendent coronary (DA, n=103) and carotid arteries (CA, n=66) in individuals under 30 years autopsied at the Legal Medical Institute of Rio de Janeiro. Histological sections, stained with hematoxilin-eosin, were classified for atherosclerosis severity accordingly to the American Heart Association. SNPs in the ECA, TNF-α (-308G/A and -238 G/A), IFN-γ (+874 A/T), MMP-9 (-1562 C/T), IL-10 (-1082 A/G and -819 C/T), NOS3 (894 G/T), ApoA1 ( rs964184 ), and ApoE (E2E3E4 isoforms) genes were genotyped by automatic sequencing. Population mean age was 26 years (107 males and 15 females). DA and CA histology showed, respectively: normal arteries in 2 and 1 cases; level I atherosclerotic lesion in 0 and 5; level II in 16 and 12; level III in 71 and 26; level IV in 6 and 19; and level V in 8 and 3 cases. Genotype distribution was as follow: ECA: 49 DD (related to high ECA levels), 18 II (related with low ECA levels) and 48 DI; TNF-α: 59 GG, 21 GA, and 8 AA at position -308 (allele A associated with high TNF-α level), and 84 GG, 3 GA, and 2 AA at position -238; INF-γ: 45 subjects with allele T (related to high INF-γ levels); MMP-9: 49 CC, 14 CT, and 3 TT; IL-10: 31 AA, 10 AG, and 7 GG at position -1082 (allele G related to high IL-10 levels), and 25 CC, 12 TC, and 15 TT at position -819; NOS3: 59 GG, 35 GT, and 0 TT; ApoA1: 55 CC, 39 CG, and 0 GG; ApoE: 56 E3E3, 30 E3E4, 12 E2E3, 1 E2E4, and 1E4E4. IFN-γ and IL-10 (-1082 A/G) were significantly related to atherosclerotic severity in DA artery, while no association was observed for CA. In conclusion, we observed a high prevalence of early atherosclerosis in young adults, with significant association of IFN-γ (p < 0.001) and IL-10 (p = 0.013) genotypes with coronary disease severity.