Effects of 5HTTLPR on cardiovascular response to an emotional stressor

To replicate a prior main effect of the serotonin transporter gene promoter (5HTTLPR) genotype on cardiovascular reactivity (CVR) and explore caregiver stress as a potential moderator of 5HTTLPR effects on CVR. On the basis of prior findings, we hypothesized that the more transcriptionally active allele variants would be associated with increased CVR.

Expression of the serotonin transporter is affected by the genotype of the 5HTTLPR (S-short and L-long forms) as well as the genotype of the SNP rs25531 within this region. Based on the combined genotypes for these polymorphisms, we designated each allele as a Hi or Lo expressing allele according to expression levels-resulting in HiHi, HiLo, and LoLo groups. We examined the relationship between 5HTTLPR genotype and CVR in 164 caregivers and 158 noncaregivers. Main effects of 5HTTLPR on baseline adjusted blood pressure (systolic and diastolic blood pressures) and heart rate (HR) reactivity were examined, along with moderation by caregiving.

The 5HTTLPR × Caregiver Stress interaction moderated both systolic blood pressure (p < .02) and HR (p < .02) reactivity. In controls, the Hi activity allelic variants were associated with greater systolic blood pressure and HR reactivity as compared with the Lo activity variants. In caregivers, 5HTTLPR genotype was not associated with CVR.

Replication in this study's control group of our prior finding that 5HTTLPR alleles associated with Hi activity are associated with increased CVR to an emotion recall stressor strengthens the case that this association is real and could be partially responsible for the increased cardiovascular disease observed in persons carrying the 5HTTLPR L allele.