Early atherosclerosis and IgG2 to bacteria are associated with FcgammaRIIa genotype in non-smokers

Involvement of low density lipoprotein (LDL) immune complexes (ICs) in atherogenesis has been proposed. Human FcgammaRIIa receptor (CD32) plays a crucial role in the phagocytosis of IgG(2) ICs and a functional point mutation 131His/Arg diminishes IgG(2) binding to the receptor.

We examined FcgammaRIIa-131His/Arg polymorphism, IgG(2) antibody titres to oxidized low-density lipoprotein (OxLDL) and Streptococcus pneumoniae cell wall polysaccharide (CWPS) and subclinical atherosclerosis in a large cohort of Finnish subjects (n = 1041).

Non-smoking subjects with homozygous 131His/His genotype had more premature atherosclerosis (P = 0.004) and higher IgG(2) to bacterial CWPS (P = 0.002) compared with other genotypes. Smoking subjects had significantly higher intima-media thickness (IMT) than that of non-smokers (P < 0.001) and genotype-dependent associations were indistinct. There was no association between FcgammaRIIa genotype and antibody titres to OxLDL.

Our data demonstrate that FcgammaRIIa 131His/Arg polymorphism is associated with subclinical atherosclerosis in non-smoking subjects. Furthermore, FcgammaRIIa genotype is associated with IgG(2) titres to bacterial CWPS, but not to OxLDL. These data propose possible involvement of FcgammaRIIa receptor in atherogenesis.