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Background  Both anxiety and elevated heart rate (HR) have been implicated in the development of hypertension. The HyperGen cohort, consisting of siblings with severe and mild hypertension, an age-matched random sample of persons from the same base populations, and unmedicated adult offspring of the hypertensive siblings (N = 1,002 men and 987 women), was analyzed for an association of the angiotenisinogen AGTM235T genotype (TT, MT, MM) with an endophenotype, heart rate (HR) in high and low anxious groups.    Methodology  The interaction of AGTM genotype with anxiety, which has been independently associated with hypertension, was investigated adjusting for age, hypertension status, smoking, alcohol consumption, beta blocker medication, body mass index, physical activity and hours of television viewing (sedentary life style).    Principal Findings  Although there was no main effect of genotype on HR in men or women, high anxious men with the TT genotype had high HR, whereas high anxious men with the MM genotype had low HR. In women, HR was inversely associated with anxiety but there was no interaction with genotype.    Conclusion/Significance  The results suggest that high anxiety in men with the TT genotype may increase risk for hypertension whereas the MM genotype may be protective in high anxious men. This type of gene x environment interaction may be one reason why genome wide association studies sometimes fail to replicate. The locus may be important only in combination with certain environmental factors.

AGT M235T Genotype/Anxiety Interaction and Gender in the HyperGEN Study