The –455G/A fibrinogen genetic polymorphism is associated with a risk of coronary artery disease only in population of young people

Krzysztof Chizynski¹, Tadeusz Pietrucha²

Summary
Objective: An elevated fibrinogen level is an independent CAD risk factor. Low fibrinogen plasma concentration is associated with low levels of coronary risk even when total or low-density lipoprotein cholesterol is high. Several polymorphisms on the b fibrinogen gene have been characterised and investigated in relation to plasma fibrinogen level. However, further studies have examined the relationship between fibrinogen genotype and atherosclerosis. From the clinical point of view, the most important are the 455-G/A and the 148-C/T polymorphisms. In this paper, we present the association of the 455-G/A Fg genotype with CAD and the impact of the 455-G/A Fg polymorphisms on younger and elderly CAD patients.
Material and methods: The study group enrolled 314 patients aged 33 to 84 yrs. (average age 54 yrs.), with angiographically concerned CAD. The control group numbered 41 patients aged 29 to 74 yrs. (average age 52 yrs.) without CAD (normal coronary arteries in angiography). Genotypes and polymorphism were determined by polymerase chain reaction amplification of genomic DNA using the following allele specific primers; sense: 5´-AGA ATT TGG GAA TGC AAT CTC TGC TAC CT -3´ and antisense: 5´-TCC TCA TTG TCG TTG ACA CCT TGG GAC -3´. After Hae III enzyme digestion, the following genotypes were detected: G/G: 575 bp, 383 bp, 343 bp, A/A: 958 bp, 343 bp and G/A: 958 bp, 575 bp, 383 bp, 343 pz. PCR products were run by electrophoresis in a 3% polyacrylamide gel.
Results: Among 314 subjects with CAD enrolled in the study, 133 (42.4%) had a genotype G/G, 153 (48.7%) had G/A and 28 (8.9%) had AA. Among 41 subjects without CAD enrolled in the study, 23 (56.1%) had genotype G/G, 17 (41.5%) had G/A and 1 (2.4%) had AA. Genotype 455-G/A Fg polymorphism was not related to the presence of CAD. Further analysis was performed after dichotomy dividing genotypes into A+ (A/A and G/A genotypes) and A- (G/G genotypes). In the case of elderly subjects, differences in genotypes (A+, A-) and alleles (A, G) distribution were observed. The elderly subjects´ A+ genotype contained no CAD risk factor. In the case of the younger subjects with CAD, a higher frequency of A+ genotypes (59% vs. 40.6%; p <0.05) and A alleles (34.1% vs. 21.9%; p <0.05) was observed. The odds ratio for having CAD among the younger levelled at 2.10 (0.99-4.46) (p <0.05) in cases of subjects with A+ genotype and 1.85 (0.99-3.44) (p <0.05) in subjects with A allele.
Conclusion: In the case of the Polish population, the 455-G/A Fg genotype is a risk factor for coronary disease only among subjects aged less than 65 yrs.

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