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

Abstract

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.

Correlation between interleukin gene polymorphisms and current prevalence and mortality rates due to novel coronavirus disease 2019 (COVID‐2019) in 23 countries

“…To test this hypothesis and to limit any confounding bias (latitude, etc. ), we focused on the countries whose IL‐6 gene polymorphisms at rs1800796 and rs1800795 loci, IL‐6R gene polymorphism at rs2228145 locus, IL‐10 gene polymorphism at rs1800896 and rs1800871 loci, IL‐17A gene polymorphism at rs2275913 and IL‐17F gene polymorphism at rs763780 loci were defined and the allele frequencies were reported in 54 studies 10–63 . We searched the literature for the interleukin gene polymorphisms determined in the populations of China, Japan, India, Spain, Mexico, Sweden, Turkey, Brazil, Russia, Poland, Italy, South Africa, Netherlands, Greece, Germany, UK, Iran, Finland, Czechia, Tunisia, Norway, Egypt, Croatia.…”

Maternal obesity and developmental programming of neuropsychiatric disorders: An inflammatory hypothesis

“…However, a recent study identified a single nucleotide polymorphism (rs2228145) influencing IL-6 receptor concentrations, as being significantly elevated in French early-onset bipolar disorder patients and trending to increase in Indian Tamil patients. This suggests a trans-ethnic association between bipolar disorder and this polymorphism (Sundaresh et al, 2019). Given the importance of these signalling molecules in development, one could hypothesise that their dysregulation through maternal obesity may contribute to increased neurodevelopmental disorder susceptibility in offspring.…”

Patients with obstructive sleep apnea have suppressed levels of soluble cytokine receptors involved in neurodegenerative disease, but normal levels with airways therapy

“…Altered levels of the membrane and/or soluble isoforms of gp130 and IL6R have been reported in the serum, cerebral fluid, and/or brain of patients with Alzheimer disease [112][113][114], amyotrophic lateral sclerosis [70], multiple sclerosis [71], and schizophrenia and bipolar disorder [72,115]. A few single nucleotide polymorphisms affecting IL6R expression levels or protein activity also correlate with ND [70,[116][117][118].…”