Evidence suggests the existence of association between a large panel of modifiable biomarkers representing inflammation, coagulation, paraoxonase, and endothelial activation pathways and carotid atherosclerosis. Thus, this study investigated whether CRP, FGA, FGB, FGG, PON1, and EDNRA gene variants affected plasma hs-CRP, fibrinogen levels, and thickness of carotid intima media thickness (IMT). Nineteen single-nucleotide polymorphisms of CRP, FGA, FGB, FGG, PON1, and EDNRA genes were examined in 480 participants from 160 families. Carotid IMT was measured by ultrasound. Generalized linear models with generalized estimating equation were utilized to consider the dependence of subjects within families. In the recessive model, homozygotes for the minor alleles of rs1800789, rs1800790 and rs4220 SNPs in FGB gene indicated a reduced risk of IMT (Exp. β = 0.89, 0.89, 0.88), which remained significant after adjustment for confounding factors. Significant interaction effects between CRP SNP rs1130864 and rs3093059 and gender for IMT were observed with a significant association in men only. Men carrying minor-minor genotype of CRP SNP rs1130864 and rs3093059 had 0.70- and 0.78-fold lower IMT than men carrying minor-major/major-major genotype. We also observed that the interaction of CRP SNP rs1130864 and rs3093059 with obesity on IMT, hs-CRP and fibrinogen levels. These results support the hypothesis that inflammatory genes are involved in atherosclerosis, most likely via complex gene-gender and gene-obesity interactions.