IL6/IL6R genetic diversity and plasma IL6 levels in bipolar disorder: An Indo-French study

Reports of association of genetic variants of IL6 and its receptor (IL6R) with psychiatric disorders are inconsistent, and there are few population-based studies thus far in bipolar disorder (BD). We genotyped the IL6 rs1800795 and IL6R rs2228145 polymorphisms in two independent sets of patients exposed to different environmental stimuli such as climatic conditions or specific infectious burden – a French sample and a south Indian Tamil sample of BD with quantitation of circulating plasma IL-6 levels in the latter sub-sample. In both populations, allele and genotype frequencies did not differ significantly between cases and controls for either polymorphism. Upon stratifying based on age at onset, we found no associations with the IL6 rs1800795 variant. However, the IL6R rs2228145 C allele and CC genotype were associated with early onset of disease in the French sample when compared to late onset BD. A similar trend was observed in the Indian population where we also found that plasma IL-6 levels were significantly higher in BD and also in patients who were in residual phase or remission both as compared to controls. Our findings are in favour of a possible trans-ethnic implication of the IL6R genetic diversity in BD and reinforce the notion that IL-6 is an important marker of the operating inflammatory processes in the disease.