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The C (–260) → T polymorphism has been reported to regulate CD14 gene expression. It has also been implicated in atherosclerotic diseases, and in addition, it could be a genetic factor responsible for interindividual differences in the susceptibility to Chlamydia pneumoniae infection. This case-control study is aimed at evaluating the association between CD14 promoter polymorphisms, frequency of persistent C pneumoniae infection, and anti–chlamydial heat shock protein 60 (cHsp60) induction in stroke patients. Persistent C pneumoniae infection was observed in 43.3% of control subjects and 53.3% of patients (P = .005). The odds ratio of persistent infection was 3.25 for the CC genotype in stroke patients (P = .018). However, the serologic positive responses to cHsp60 in people with the TT genotype were significantly lower in stroke patients (9.3% vs 38.6%; P < .001). Our findings suggest that persistent C pneumoniae infection is independently associated with stroke in CC genotypes and the lowering of cHsp60 antibody levels in TT genotypes.