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FIBRINOGEN GENETIC VARIABILITY ACCELERATES ATHEROGENESIS BY ALTERING THE INFLAMMATORY PROCESS AND COAGULATION IN PATIENTS WITH DIABETES MELLITUS TYPE 2 AND HYPERTENSION
Author(s): ,
Zoi Pallantza
Affiliations:
Athens Ippokratio Hospital,Athens,Greece
,
Nikolaos Papageorgiou
Affiliations:
Athens Ippokratio Hospital,Athens,Greece
,
Maria Kozanitou
Affiliations:
Athens Ippokratio Hospital,Athens,Greece
,
Dennis Goubini
Affiliations:
Athens Ippokratio Hospital,Athens,Greece
,
Panagiota Parigori
Affiliations:
Athens Ippokratio Hospital,Athens,Greece
,
Lydia Plavoukou
Affiliations:
Athens Ippokratio Hospital,Athens,Greece
,
Giorgos Mallios
Affiliations:
Athens Ippokratio Hospital,Athens,Greece
,
Basiliki Palioura
Affiliations:
Athens Ippokratio Hospital,Athens,Greece
,
Maria Karagrigoriou
Affiliations:
Athens Ippokratio Hospital,Athens,Greece
,
Christodoulos Stefanadis
Affiliations:
Athens Ippokratio Hospital,Athens,Greece
Dimitris Tousoulis
Affiliations:
Athens Ippokratio Hospital,Athens,Greece
(Abstract release date: 05/19/16) EHA Library. Pallantza Z. 06/09/16; 133108; E1559
Dr. Zoi Pallantza
Dr. Zoi Pallantza
Contributions
Abstract
Abstract: E1559

Type: Eposter Presentation

Aims
Hypertension (HTN) and diabetes mellitus (DM) are significant risk factors for atherosclerosis and characterised by altered coagulation and inflammatory process. In the present study 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 polymerase chain reaction-restriction fragment length polymorphism (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).

Conclusion
The AA homozygosity (rs180070) was associated with higher IL-6 levels and CD40L concentrations. We also showe for the first time, to our knowledge, that the AA homozygosity (rs180070) is associated with increased D-dimer levels. Our results of this study showed that higher levels of fibrinogen were associated with elevated D-dimer levels. Homozygotic status for the rs180070 polymorphism was also related to higher D-dimer levels both in HTN and DM patients.

Session topic: E-poster

Keyword(s): Fibrinogen
Abstract: E1559

Type: Eposter Presentation

Aims
Hypertension (HTN) and diabetes mellitus (DM) are significant risk factors for atherosclerosis and characterised by altered coagulation and inflammatory process. In the present study 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 polymerase chain reaction-restriction fragment length polymorphism (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).

Conclusion
The AA homozygosity (rs180070) was associated with higher IL-6 levels and CD40L concentrations. We also showe for the first time, to our knowledge, that the AA homozygosity (rs180070) is associated with increased D-dimer levels. Our results of this study showed that higher levels of fibrinogen were associated with elevated D-dimer levels. Homozygotic status for the rs180070 polymorphism was also related to higher D-dimer levels both in HTN and DM patients.

Session topic: E-poster

Keyword(s): Fibrinogen

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