Assessment of the Genetic Susceptibility to Chronic Inflammation in MetS through an IL-6 and IL-6R Genes Polymorphism Survey in the Congolese Black African Population
Background: Chronic inflammation appears to be a pivotal mechanism underlying the pathophysiology of metabolic syndrome (MetS). Increasing evidence highlights the role of cytokines and their receptors gene polymorphisms in the susceptibility to the chronic inflammatory state observed in MetS. Since we recently showed combination of hs-CRP and IL-6 dosages improved MetS diagnosis accuracy and provided that IL-6/IL-6R gene polymorphisms appear to play a role in susceptibility to MetS, we aimed at investigating the role of some IL-6 and IL-6R receptor SNPs in the genetic susceptibility to chronic inflammation in this debilitating syndrome. Methods: A total of 319 Congolese adults (93 with MetS and 226 without MetS) were recruited for this population-based cross-sectional study. The NCEP-ATPIII criteria were used to define MetS. DNA extracted from whole blood was used for genotyping IL-6 (-174G/C, -597G/A) and IL-6R (+48867A/C) gene polymorphisms by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) technique. Serum hs-CRP and IL-6 levels were measured using the immunoturbidimetric and ELISA methods. Results: To our knowledge, our study is the first one to assess the genetic susceptibility to chronic inflammation in MetS through an IL-6 and IL-6R genes polymorphism survey in a black African population. In men, IL-6 (-174G/C) heterozygous genotype GC was found to be significantly associated with MetS but very interestingly in women, IL-6R (+48867A/C) polymorphism was, on the contrary, linked to the pathology with a strong association for heterozygous AC genotype. Finally, the IL-6 (-174G/C, -597G/A) and IL-6R (+48867A/C) CAC haplotype were indistinctly associated with MetS. This shows that observed gender differences in MetS susceptibility might at least partially be related to differing gender responses to inflammation gene polymorphism. Conclusion: For the first time here, our findings unravel a possible association between IL-6R (+48867A/C) polymorphism and MetS in the adult Congolese population. More interestingly, the IL-6 (-174G/C, -597G/A) and IL-6R (+48867A/C) CAC haplotype appears to be related to MetS genetic susceptibility, highlighting the contribution of this SNPs combination in the settlement and/or development of this inflammatory condition possibly alongside with others factors.
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