Background People of South Asian descent are more prone to develop cardiovascular diseases coinciding with higher mortality as compared to Europids. Recently, a meta-analysis showed that the anti-diabetic glucagon-like peptipe-1 receptor (GLP1R) agonists improve cardiovascular outcomes. Preclinical studies suggest that GLP1 enhancing strategies reduce atherosclerosis development by inducing anti-inflammatory effects rather than improving dyslipidemia. However, in humans the effects of GLP1R agonism on the immune system remain to be determined. Therefore, the aim of this study was to examine the effect of the GLP1R agonist exenatide on immune gene expression in human blood. Secondly we were interested if there was a difference in expression of immune genes between healthy South Asians and Europids.

Methods Fasted blood samples were obtained before and after 12 weeks exenatide treatment (2 mg/week subcutaneous), from 23 healthy lean men from South Asian (n=12; age 27.5 ± 3.2 years) and Europid (n=11; age 25.8 ± 3.3 years) descent. We measured mRNA expression of immune genes in blood using a dual-color reverse transcriptase multiplex ligation-dependent probe amplification (dcRT-MLPA) assay.

Results Exenatide treatment did not affect immune gene expression in neither the South Asian group, nor the Europid group, nor after pooling of both groups. Interestingly, before treatment, expression levels of NLRC4 (-29% P=0.03), NLRP10 (-18% P=0.02), NLRP2 (-40% P=0.04), and NLRP7 (-15% P=0.03) were significantly lower in South Asians compared to Europids. In addition, NLRP3 tended to be lower in South Asians (-14%, P=0.06).

Conclusion Exenatide treatment did not change immune gene expression in blood of healthy South Asian and Europid men. Notably, on baseline expression of the pro-inflammatory inflammasome components were significantly lower in healthy South Asians compared to Europids, which warrants further investigation.