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

Authors :
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
Agyenim-Boateng, Kofi
Acheampong, Joseph
Adebamowo, Clement
Herbert, Alan
Gerry, Norman
Christman, Michael
Source :
Immunogenetics; May2012, Vol. 64 Issue 5, p351-359, 9p
Publication Year :
2012

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) with eight SNPs, the most significant of which was rs5743185 in the PMS1 gene ( p = 2.30 × 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), ten SNPs in the IL-1 gene family ( IL1F5, IL1F8, IL1F10, and IL1Ra, p = 1.04 × 10 to 1.75 × 10), and 23 SNPs near the IL1A gene ( p = 1.22 × 10 to 1.63 × 10). 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). 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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00937711
Volume :
64
Issue :
5
Database :
Complementary Index
Journal :
Immunogenetics
Publication Type :
Academic Journal
Accession number :
74188191
Full Text :
https://doi.org/10.1007/s00251-011-0596-7