β-Fibrinogen −455G>A (rs1800790) in a sample of Libyan Patients with Cardiovascular Disease: A Pilot Study with Hardy–Weinberg Assessment

Abstract

A B S T R A C T

Background: Cardiovascular and thromboembolic diseases are major contributors to morbidity in Libya, yet the distribution and potential relevance of coagulation-related genetic variants—including the β-fibrinogen −455G>A promoter polymorphism (rs1800790)—remain poorly characterized in North African populations.

Aims: To provide a preliminary descriptive characterization of rs1800790 in Libyan patients with cardiovascular disease, and to document the methodological considerations—principally Hardy–Weinberg equilibrium (HWE) deviation and treatment confounding—that should inform future adequately powered studies.

Methods: This descriptive case series was conducted at Al Fouad Cardiac Center, Tripoli, Libya, between April and August 2025. Forty-four Libyan patients with established cardiovascular disease were included. rs1800790 was genotyped using the CVD StripAssay (ViennaLab Diagnostics GmbH). Genotyping succeeded at first pass in 38 of 44 patients; the remaining six were repeated once from the same DNA and all gave interpretable results. HWE was assessed by an exact test. Four imputed D-dimer entries were identified and excluded. Three post hoc exploratory comparisons by genotype (coronary artery disease, coronary stenting, and D-dimer >1.0 µg/mL) used Fisher's exact test with a single Haldane–Anscombe-corrected odds ratio estimator and Bonferroni correction (α = 0.0167).

 Results: Only G/G (16; 36.4%) and G/A (28; 63.6%) genotypes were observed. The genotype distribution deviated from HWE (conditional exact P = 0.0017; Pearson χ² = 9.58, 1 df, P = 0.0020), with a heterozygote excess and absent A/A homozygotes. This is reported as a quality-control finding requiring investigation, not as proof of assay failure. Among the 40 patients with a measured D-dimer, a value >1.0 µg/mL was more frequent in G/A than G/G patients (14/24, 58.3% vs 1/16, 6.3%; corrected OR 14.3, 95% CI 2.2–91.2; Fisher's exact P = 0.0009), and this survived Bonferroni correction. Coronary artery disease (85.7% vs 56.3%; corrected OR 4.30; P = 0.067) and coronary stenting (64.3% vs 37.5%; corrected OR 2.85; P = 0.12) did not differ significantly. Lipid values were treatment-confounded, with 88.6% of patients receiving statins.

 Conclusions: This report offers preliminary genotype data for rs1800790 in Libyan patients with cardiovascular disease. The HWE deviation, absence of A/A homozygotes, lack of an age-comparable control group and absence of orthogonal validation mean that the results are hypothesis-generating only. The post hoc association with raised D-dimer warrants confirmation in a larger, validated, case–control study.