Genetic polymorphisms of angiotensin-2 type 1 receptor and angiotensinogen and risk of renal dysfunction and coronary heart disease in type 2 diabetes mellitus

<p>Abstract</p> <p>Background</p> <p>Increased activation of the renin-angiotensin system (RAS) may be important in promoting coronary heart disease (CHD) and renal dysfunction, but limited data are available on associations between angiotensin type 1 receptor (<it>AGT1R</it>) and angiotensinogen (<it>AGT</it>) genotypes in type 2 diabetes.</p> <p>Methods</p> <p>Study participants were diabetics from the Health Professionals Follow-Up Study (HPFS) and the Nurses' Health Study (NHS). We analyzed single nucleotide polymorphisms (SNPs) associated with cardiovascular pathophysiology (including <it>AGT1R </it>T573C, <it>AGT1R </it>A1166C, and <it>AGT </it>M235T) and presence of renal dysfunction (eGFR<60 ml/min/1.73 m²) or history of CHD.</p> <p>Results</p> <p>The <it>AGT1R </it>1166 C-allele was associated with eGFR<60 ml/min/1.73 m²(multivariable OR 1.63 [1.01, 2.65]) in the HPFS men (n = 733) and in the combined dataset (n = 1566) (OR 1.42 [1.02, 1.98]). The <it>AGT1R </it>1166 C-allele was also associated with CHD in men (OR 1.57 [1.10, 2.24]). In NHS women (n = 833), <it>AGT </it>235T-allele was associated with CHD (OR 1.72 [1.20, 2.47]). Removal of hypertension from the fully adjusted models did not influence results, suggesting that the associations may not be mediated by hypertension. There were significant interactions between sex and <it>AGT1R </it>1166 C-allele (p = 0.008) and <it>AGT </it>M235T (p = 0.03) in models for CHD. No significant associations were seen between <it>AGT1R </it>T573 C-allele and renal dysfunction or CHD.</p> <p>Conclusion</p> <p>Polymorphisms in <it>AGT1R </it>and <it>AGT </it>genes are associated with renal dysfunction and CHD in type 2 diabetes and further support the important role of the RAS in these complications. Sex may modify associations between <it>AGT1R </it>1166 C-allele and <it>AGT </it>235T and CHD in type 2 diabetes.</p

Action ability modulates time‑to‑collision judgments

Time-to-collision (TTC) underestimation has been interpreted as an adaptive response that allows observers to have more time to engage in a defensive behaviour. This bias seems, therefore, strongly linked to action preparation. There is evidence that the observer’s physical fitness modulates the underestimation effect so that people who need more time to react (i.e. those with less physical fitness) show a stronger underestimation effect. Here we investigated whether this bias is influenced by the momentary action capability of the observers. In the first experiment, participants estimated the time-to-collision of threatening or non-threatening stimuli while being mildly immobilized (with a chin rest) or while standing freely. Having reduced the possibility of movement led participants to show more underestimation of the approaching stimuli. However, this effect was not stronger for threatening relative to non-threatening stimuli. The effect of the action capability found in the first experiment could be interpreted as an expansion of peripersonal space (PPS). In the second experiment, we thus investigated the generality of this effect using an established paradigm to measure the size of peripersonal space. Participants bisected lines from different distances while in the chin rest or standing freely. The results replicated the classic left-to-right gradient in lateral spatial attention with increasing viewing distance, but no effect of immobilization was found. The manipulation of the momentary action capability of the observers influenced the participants’ performance in the TTC task but not in the line bisection task. These results are discussed in relation to the different functions of PPS