| Fatty acids (FA) in obese individuals bind to toll like-receptor 4 (TLR4) on peripheral adipose tissue (AT) macrophages to activate nuclear factor kappa B (NFkB) and initiate an inflammatory response. Subsequently, this may result in upregulation of inflammatory biomarkers such as IL- 6 and TNF- alpha. This study examined the hypothesis that genetic polymorphisms in v-rel reticuloendotheliosis viral oncogene homologue A (avian) ( RELA) and inhibitor of kappa light polypeptide gene enhancer on B- cell kinase Beta (IKBKB) are associated with IL-6, IL-10, and TNF- alpha expression in a cohort of obese African Americans. RELA and IKBKB are genes that encode for NFkB and I kappa B kinase- Beta (IKK-Beta) respectively. The study sample comprised of 578 subjects (mean age 43.5 years, 72 % women) from the Howard University Family Study (HUFS). DNA samples were genotyped for 6 RELA and 11 IKBKB tagSNPs using the Sequenom platform. Circulating IL-6, IL-10, and TNF- alpha plasma levels were quantitated, using Quantikine HS ELISA assays (R&D systems). Genetic association analysis was performed with linear regression models, adjusting for covariates as necessary. Real-time polymerase chain reaction (RT-PCR) was used to quantitate RELA, IKBKB, IL-6, IL-10, and TNF- alpha transcript levels in omental AT samples from African Americans. The results showed that percent fat mass (PFM) was associated with IKBKB SNP rs3747811. IL-6 levels were associated with IKBKB SNP rs12334451 while IL-10 levels were associated with IKBKB SNPs rs4560769 and rs3747811. TNF-alpha levels were also significantly associated with IKBKB SNPs rs16891227 and rs178757378 as well as RELA SNP rs11227247. RELA, IKBKB, IL -10, and TNF-alpha genes were expressed 3-4 fold higher in obese AT in comparison to non-obese controls. On the other hand, IL-6 showed higher expression in adipose tissue from non-obese controls. These results suggest that RELA and IKBKB genetic variants may serve as genetic markers in the obesity-induced inflammation. Also, RELA, IKBKB, IL-6, IL-10 and TNF-alpha were differentially expressed in obese and non-obese AT. Inclusive, these results suggest that RELA and IKBKB variants are associated with the obesity-inflammation relationship. |
