The - 148 C/T fibrinogen gene polymorphism and fibrinogen levels in ischaemic stroke: a case-control study

Abstract

Background: To determine whether 2148 C/T fibrinogen gene promoter polymorphism increases stroke risk by modifying the fibrinogen level. Design: A case-control study of patients with first ever ischaemic stroke, confirmed by computed tomography. Methods: Venous blood samples were collected for fibrinogen and routine coagulation tests one week after the stroke, and after three months in about half the patients. Population controls were age and sex matched. 2148 C/T fibrinogen polymorphism was determined by polymerase chain reaction followed by digestion with restriction enzymes HindIII/AluI. Results: There were 124 patients and 125 controls, mean age 56 years (range 18 to 75); 34 patients (27%) and 41 controls (33%) were heterozygous for 2148 C/T fibrinogen polymorphism; six patients (5%) and five controls (4%) had the T/T genotype. The odds ratio of ischaemic stroke associated with CC homozygotes v T carriers was 0.8 (95% confidence interval, 0.5 to 1.4). Relative risk for ischaemic stroke associated with fibrinogen levels in the highest quartile was 3.9 (1.9 to 8.4) at one week, decreasing to 1.4 (0.6 to 3.3) at three months. Conclusions: 2148 C/T fibrinogen gene polymorphism was not a strong risk factor for ischaemic stroke. High fibrinogen levels early after acute stroke probably represent an acute phase response.

Fibrinogen gene variation and ischemic stroke

“…Consistent with what has previously been reported, we found a strong correlation between fibrinogen and CRP concentration [29], a decrease in fibrinogen concentration during follow-up [5,17,20], and an association between acute plasma fibrinogen and stroke severity [20,29]. This may suggest that increased plasma fibrinogen in stroke merely reflects an inflammatory response to the event.…”

“…Results indicate that the FGA and FGG genes may be of importance [13,14]. In contrast, several studies have investigated the possible association between fibrinogen gene polymorphisms, plasma fibrinogen level, and ischemic stroke, as well as coronary heart disease [15][16][17][18][19][20][21][22]. Although many studies have reported an association between FGB gene polymorphism and plasma fibrinogen, results have been inconsistent with respect to cardiovascular and cerebrovascular events [22].…”

“…In stroke, the focus has mainly been on two putative functional promotor single nucleotide polymorphisms (SNPs) in the FGB gene, which are in complete linkage disequilibrium (i.e. the fibrinogen )455 G/A (rs1800790) and the )148 C/T (rs1800787) SNPs) [15][16][17][18]. Data on other fibrinogen SNPs in relation to stroke are very limited [18][19][20].…”

Fibrinogen γ′ in Ischemic Stroke

“…The study design has been described previously. 6 Baseline characteristics are given in Table 1. Blood was collected from an unselected subgroup of 47 patients 7 to 14 days (acute phase) and 3 months after the stroke in tubes containing 1/10 volume of 0.129 mol/L sodium citrate.…”

Is Plasma Fibrinogen Useful in Evaluating Ischemic Stroke Patients?

“…20 These include animal studies suggesting that fibrinogen has an intrinsically central nervous system toxicity, 21 promoting apoptosis, 22 neurodegeneration 23 and an inhibition of functional recovery after injury. 24 High fibrinogen concentrations provide additional information about risk, even if it is simply a bystander of the inflammatory response in ischemic stroke and transient ischemic attack.…”