Fibrinogen Beta-Chain -C148T Polymorphism is Associated with Increased Fibrinogen, C-Reactive Protein, and Interleukin-6
- PDF / 143,094 Bytes
- 7 Pages / 595.276 x 790.866 pts Page_size
- 19 Downloads / 188 Views
Fibrinogen Beta-Chain -C148T Polymorphism is Associated with Increased Fibrinogen, C-Reactive Protein, and Interleukin-6 in Patients Undergoing Coronary Artery Bypass Grafting Ewa Wypasek,1,2,3 Ewa Stepien,1,2 Malgorzata Kot,1 Dariusz Plicner,1,2 Boguslaw Kapelak,1,2 Jerzy Sadowski,1,2 and Anetta Undas1,2
Abstract—The fibrinogen beta-chain (FGB) -C148T polymorphism is linked with plasma fibrinogen concentration in the general population. We examined whether the -C148T polymorphism is associated with pre- and early postoperative levels of fibrinogen, C-reactive protein (CRP), and interleukin-6 (IL-6) in 243 consecutive patients undergoing coronary artery bypass grafting (CABG) surgery. Plasma inflammatory markers were measured prior to and 5–7 days after surgery. The -C148T polymorphism was analyzed with the restriction fragment-length polymorphism method. The genotype distribution was as follows: CC—142 (58%), CT—85 (35%), and TT—16 (7%). Carriers of the -148T allele had higher preoperative plasma fibrinogen (4.42±0.14 vs. 4.07±0.11 mg/L, p=0.04) and CRP levels (7.49±1.2 vs. 4.26±1.0 mg/L, p=0.04) compared with non-carriers; 5 to 7 days after CABG, patients carrying -148T allele had increased CRP (70.4±5.0 vs. 51.6±4.25 mg/L, p=0.005) and IL-6 levels (22.34±2.64 vs. 15.53±2.28 pg/L, p=0.05), but not fibrinogen, compared with the remaining subjects. In-hospital nonfatal stroke occurred more frequently in -148T allele carriers (4% vs. 0%, p=0.02). No genotype-associated differences were found in the occurrence of postoperative myocardial infarction and death. Presence of the -148T allele has also been associated with longer intensive care stay and intubation time (p=0.01). Multivariate analysis identified the CT+TT genotype as an independent predictor of pre- and postoperative CRP levels. The results indicate that the presence of the -148T FGB allele determines higher pre- and postoperative levels of inflammatory markers, which might be associated with in-hospital clinical outcomes. KEY WORDS: CABG; -C148T FGB polymorphism; inflammation; CRP; fibrinogen; IL-6.
β-fibrinogen promoter [2]. One of the polymorphisms identified within this region is -C148T mutation located close to an interleukin-6-response element affecting fibrinogen gene expression, mainly in response to the acute-phase reaction [3]. This polymorphism is in complete allelic association with -G455A in white population [4]. Several studies have shown that a -C148T polymorphism is associated with increased plasma fibrinogen levels in men and women in the general population [5–7]. Fibrinogen conversion to fibrin is the final step in the blood coagulation. Moreover, fibrinogen acts as a bridging molecule for many types of cell–cell adhesion events critical in atherogenesis [8]. Fibrinogen synthesis is upregulated primarily by interleukin-6 (IL-6) which controls the hepatic production
INTRODUCTION Fibrinogen is encoded by three separate genes located in a 50-Kb cluster on the long arm of chromosome 4, which encode for the α, β, and γ chains [1]. The rate limiting step in fibr
Data Loading...
