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Abstract 16388: Fibrinogen Genetic Variants Promote Atherosclerosis by Altering the Inflammatory Process and Coagulation in Patients With Essential Hypertension and Diabetes Mellitus


 Introduction:
 Hypertension (HTN) and diabetes mellitus (DM) are associated with atherosclerosis and affect coagulation and inflammation.
 
 
 Hypothesis:
 We aimed to investigate the role of fibrinogen genetic variants (rs180070 and rs2070011) on coagulation and inflammation in patients with combined DM and HTN.
 
 
 Methods:
 744 subjects (HTN and DM) were enrolled in our study. Fibrinogen polymorphisms were determined by PCR-RFLP technique. Fibrinogen, interleukin-6 (IL-6), high sensitivity C-reactive protein (hsCRP) CD40L, D-dimers and factors V, X activity were measured with appropriate laboratory methods.
 
 
 Results:
 In HTN patients, hsCRP levels were higher in the group of patients with higher fibrinogen levels compared to patients with lower and intermediate fibrinogen levels [0.28(0.12-0.42) vs 0.17(0.04-0.38) vs 0.18 (0.09-0.39), p=0.032)]. In addition, we found a significant effect of the rs180070 polymophism on IL-6 levels among HTN and DM. In HTN, IL-6 levels were higher in AA homozygotes of the rs180070 compared to all other genotypes (AG or GG) (4.96±0.69 vs 3.7±0.2, p=0.046). Similarly, DM patients homozygotes for the A allele (rs180070) had higher IL-6 levels (6.72±0.99 vs 4.01±0.35, p=0.016). In multivariable analysis, the only independent predictor of IL-6 levels in DM was the AA genotype [β(SE): 0.216 (1.76), P = 0.047]. In hypertensives, AA (rs180070) homozygosity was the only adjusted independent predictor of IL-6 levels [β(SE): 0.151 (0.642), P = 0.032]. Subgroup analysis of HTN and DM patients did not reveal any differences of CD40L levels in the presence of AA genotype (rs180070) (p=0.919 for DM and p=0.144 for HTN). We did not observe any significant change in IL-6 or CD40L levels with the presence of the AA genotype of the rs2070011 among the studied subgroups. Finally, we found that the AA homozygosity (rs180070) was associated with increases D-dimer levels in both DM and HTN (DM: 741.6±109,4 vs 487.3±35.6, p=0.028, HTN 623.3±79.6 vs 388.6±23.5, p=0.048).
 
 
 Conclusions:
 The AA homozygosity (rs180070) was associated with higher IL-6 levels and CD40L. We demonstrated for the first time, that the AA homozygosity (rs180070) is associated with increased D-dimer levels. These were also associated with higher fibrinogen levels.
