Background

Chronic low-grade inflammation, characterized by elevated plasma levels of C-reactive protein (CRP), has been inversely associated with dispositional optimism. Using a Mendelian randomization design, this study explores whether CRP haplotypes that determine CRP plasma levels are also associated with dispositional optimism.

Methods

In a sample of 1,084 community-dwelling subjects (aged 60-85 years) from three cohort studies (Arnhem Elderly Study, n = 426; Leiden Longevity Study, n = 355; Zutphen Elderly Study, n = 303), six CRP polymorphisms (rs2808628, rs2808630, rs1205, rs1800947, rs1417938, and rs3091244) coding for five common haplotypes were genotyped. The association of CRP haplotypes with CRP plasma levels and dispositional optimism was analyzed using multivariable linear regression models. Subanalyses were stratified by body mass index (BMI ≥25 kg/m(2)).

Results

CRP haplotypes determined CRP plasma levels (adjusted β = 0.094, p < 0.001). In the whole group, no association was found between CRP haplotypes and dispositional optimism scores (adjusted β = -0.02, p = 0.45). In BMI strata, CRP haplotypes were associated with increasing levels of plasma CRP levels (adjusted β = 0.112; p = 0.002) and lower dispositional optimism levels (adjusted β = -0.068; p = 0.03) in the obese group only.

Conclusions

These results suggest that genetically increased CRP levels are involved in low dispositional optimism, but only in case of obesity.