Genome-wide associated loci influencing interleukin (IL)-10, IL-1Ra, and IL-6 levels in African Americans

dc.contributor.authorTekola Ayele, F
dc.contributor.authorHuang, H
dc.contributor.authorZhou, J
dc.contributor.authorDoumatey, A
dc.contributor.authorJohnson, T
dc.contributor.authorRotimi, C
dc.contributor.authorFasanmade, O
dc.date.accessioned2019-11-18T08:16:34Z
dc.date.available2019-11-18T08:16:34Z
dc.date.issued2012-05
dc.descriptionStaff publicationsen_US
dc.description.abstractInterleukins (ILs) are key mediators of the immune response and inflammatory process. Plasma levels of IL-10, IL-1Ra, and IL-6 are associated with metabolic conditions, show large inter-individual variations, and are under strong genetic control. Therefore, elucidation of the genetic variants that influence levels of these ILs provides useful insights into mechanisms of immune response and pathogenesis of diseases. We conducted a genome-wide association study (GWAS) of IL-10, IL-1Ra, and IL-6 levels in 707 non-diabetic African Americans using 5,396,780 imputed and directly genotyped single nucleotide polymorphisms (SNPs) with adjustment for gender, age, and body mass index. IL-10 levels showed genome-wide significant associations (p  < 5 × 10(-8)) with eight SNPs, the most significant of which was rs5743185 in the PMS1 gene (p = 2.30 × 10(-10)). We tested replication of SNPs that showed genome-wide significance in 425 non-diabetic individuals from West Africa, and successfully replicated rs17365948 in the YWHAZ gene (p = 0.02). IL-1Ra levels showed suggestive associations with two SNPs in the ASB3 gene (p = 2.55 × 10(-7)), ten SNPs in the IL-1 gene family (IL1F5, IL1F8, IL1F10, and IL1Ra, p = 1.04 × 10(-6) to 1.75 × 10(-6)), and 23 SNPs near the IL1A gene (p = 1.22 × 10(-6) to 1.63 × 10(-6)). We also successfully replicated rs4251961 (p = 0.009); this SNP was reported to be associated with IL-1Ra levels in a candidate gene study of Europeans. IL-6 levels showed genome-wide significant association with one SNP (RP11-314E23.1; chr6:133397598; p = 8.63 × 10(-9)). To our knowledge, this is the first GWAS on IL-10, IL-1Ra, and IL-6 levels. Follow-up of these findings may provide valuable insight into the pathobiology of IL actions and dysregulations in inflammation and human diseases.en_US
dc.identifier.citationTekola Ayele F, Doumatey A, Huang H, Zhou J, Charles B, Erdos M, Adeleye J, Balogun W, Fasanmade O, Johnson T, Oli J, Okafor G, Amoah A, Eghan BA Jr, Agyenim-Boateng K, Acheampong J, Adebamowo CA, Herbert A, Gerry N, Christman M, Chen G, Shriner D, Adeyemo A, Rotimi CN. Genome-wide associated loci influencing interleukin (IL)-10, IL-1Ra, and IL-6 levels in African Americans. Immunogenetics. 2012 May;64(5):351-9. doi: 10.1007/s00251-011-0596-7en_US
dc.identifier.issn00937711, 14321211
dc.identifier.otherdoi: 10.1007/s00251-011-0596-7
dc.identifier.urihttps://ir.unilag.edu.ng/handle/123456789/6885
dc.language.isoenen_US
dc.publisherSpringeren_US
dc.relation.ispartofseriesImmunogenetics;Vol.64(5)
dc.subjectAfrican Americansen_US
dc.subjectGWASen_US
dc.subjectResearch Subject Categories::MEDICINEen_US
dc.titleGenome-wide associated loci influencing interleukin (IL)-10, IL-1Ra, and IL-6 levels in African Americansen_US
dc.typeArticleen_US
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