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

Content Provider	Springer Nature Link
Author	Tekola Ayele, Fasil Doumatey, Ayo Huang, Hanxia Zhou, Jie Charles, Bashira Erdos, Michael Adeleye, Jokotade Balogun, Williams Fasanmade, Olufemi Johnson, Thomas Oli, Johnnie Okafor, Godfrey Amoah, Albert Eghan, Benjamin A. Agyenim Boateng, Kofi Acheampong, Joseph Adebamowo, Clement A. Herbert, Alan Gerry, rman Christman, Michael Chen, Guanjie Shriner, Daniel Adeyemo, Adebowale Rotimi, Charles N.
Copyright Year	2011
Abstract	Interleukins (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.
Starting Page	351
Ending Page	359
Page Count	9
File Format	PDF
ISSN	00937711
Journal	Immunogenetics
Volume Number	64
Issue Number	5
e-ISSN	14321211
Language	English
Publisher	Springer-Verlag
Publisher Date	2011-12-29
Publisher Place	Berlin, Heidelberg
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Interleukin Interleukin-10 Interleukin-1Ra Interleukin-6 Genome-wide association study African American Human Genetics Allergology Cell Biology Gene Function Immunology
Content Type	Text
Resource Type	Article
Subject	Genetics Immunology

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