Browsing by Author "Ayele, F.T."

Filter results by typing the first few letters
Now showing 1 - 2 of 2
  • No Thumbnail Available
    Item
    C-reactive protein (CRP) promoter polymorphisms influence circulating CRP levels in a genome-wide association study of African Americans
    (Human Molecular Genetics, 2012-07) Doumatey, A.P.; Chen, G.; Ayele, F.T.; Zhou, J.; Erdos, M.; Shriner, D.; Huang, H.; Adeleye, J.; Balogun, W.; Fasanmade, O.; Johnson, T.; Oli, J.; Okafor, G.; Amoah, A.; Eghan, B.A.; Agyenim-Boateng, K.; Acheampong, J.; Adebamowo, C.; Gerry, N.P.; Christman, M.F.; Adeyemo, A.; Rotimi, C.N.
    C-reactive protein (CRP) is an acute phase reactant protein produced primarily by the liver. Circulating CRP levels are influenced by genetic and non-genetic factors, including infection and obesity. Genome-wide association studies (GWAS) provide an unbiased approach towards identifying loci influencing CRP levels. None of the six GWAS for CRP levels has been conducted in an African ancestry population. The present study aims to: (i) identify genetic variants that influence serum CRP in African Americans (AA) using a genome-wide association approach and replicate these findings in West Africans (WA), (ii) assess transferability of major signals for CRP reported in European ancestry populations (EA) to AA and (iii) use the weak linkage disequilibrium (LD) structure characteristic of African ancestry populations to fine-map the previously reported CRP locus. The discovery cohort comprised 837 unrelated AA, with the replication of significant single-nucleotide polymorphisms (SNPs) assessed in 486 WA. The association analysis was conducted with 2 366 856 genotyped and imputed SNPs under an additive genetic model with adjustment for appropriate covariates. Genome-wide and replication significances were set at P < 5 × 10-8 and P < 0.05, respectively. Ten SNPs in (CRP pseudogene-1) CRPP1 and CRP genes were associated with serum CRP (P = 2.4 × 10-09 to 4.3 × 10-11). All but one of the top-scoring SNPs associated with CRP in AA were successfully replicated in WA. CRP signals previously identified in EA samples were transferable to AAs, and we were able to fine-map this signal, reducing the region of interest from the 25 kb of LD around the locus in the HapMap CEU sample to only 8 kb in our AA sample.
  • No Thumbnail Available
    Item
    Genome-wide associated loci influencing interleukin (IL)-10, IL-1Ra, and IL-6 levels in African Americans
    (Immunogenetics, 2012-05) Ayele, F.T.; 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 Jr., B.A.; Agyenim-Boateng, K.; Acheampong, J.; Adebamowo, C.A.; Herbert, A.; Gerry, N.; Christman, M.; Chen, G.; Shriner, D.; Adeyemo, A.; Rotimi, C.N.
    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 nondiabetic 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.