OBJECTIVE: We previously reported an analysis of single-nucleotide polymorphisms (SNPs) in 3 validated European rheumatoid arthritis (RA) susceptibility loci, TAGAP, TNFAIP3, and CCR6, in African American patients with RA. Unexpectedly, the disease-associated alleles were different in African Americans from those in Europeans. In an effort to better define their contribution, we performed additional SNP genotyping in these genes. METHODS: Seven SNPs were genotyped in 446 African American patients with RA and in 733 African American control subjects. Differences in minor allele frequency between the RA cases and controls were analyzed after controlling for the global proportion of European admixture, and pairwise linkage disequilibrium (LD) was estimated among the SNPs. RESULTS: Three SNPs were significantly associated with RA: the TNFAIP3 rs719149 A allele (OR 1.22 [95% confidence interval (95% CI) 1.03-1.44], P = 0.02), the TAGAP rs1738074 G allele (OR 0.75 [95% CI 0.63-0.89, P = 0.0012), and the TAGAP rs4709267 G allele (OR 0.74 [95% CI 0.60-0.91], P = 0.004). Pairwise LD between the TAGAP SNPs was low (r(2) = 0.034). The haplotype containing minor alleles for both TAGAP SNPs was uncommon (4.5%). After conditional analysis of each TAGAP SNP, its counterpart remained significantly associated with RA (rs1738074 for rs4709267 P = 0.00001 and rs4709267 for rs1738074 P = 0.00005), suggesting independent effects. CONCLUSION: SNPs in regulatory regions of TAGAP and an intronic SNP (TNFAIP3) are potential susceptibility loci in African Americans. Pairwise LD, haplotype analysis, and SNP conditioning analysis suggest that these 2 SNPs in TAGAP are independent susceptibility alleles. Additional fine-mapping of this gene and functional genomic studies of these SNPs should provide further insight into the role of these genes in RA.
OBJECTIVE: We previously reported an analysis of single-nucleotide polymorphisms (SNPs) in 3 validated European rheumatoid arthritis (RA) susceptibility loci, TAGAP, TNFAIP3, and CCR6, in African American patients with RA. Unexpectedly, the disease-associated alleles were different in African Americans from those in Europeans. In an effort to better define their contribution, we performed additional SNP genotyping in these genes. METHODS: Seven SNPs were genotyped in 446 African American patients with RA and in 733 African American control subjects. Differences in minor allele frequency between the RA cases and controls were analyzed after controlling for the global proportion of European admixture, and pairwise linkage disequilibrium (LD) was estimated among the SNPs. RESULTS: Three SNPs were significantly associated with RA: the TNFAIP3rs719149 A allele (OR 1.22 [95% confidence interval (95% CI) 1.03-1.44], P = 0.02), the TAGAPrs1738074 G allele (OR 0.75 [95% CI 0.63-0.89, P = 0.0012), and the TAGAPrs4709267 G allele (OR 0.74 [95% CI 0.60-0.91], P = 0.004). Pairwise LD between the TAGAP SNPs was low (r(2) = 0.034). The haplotype containing minor alleles for both TAGAP SNPs was uncommon (4.5%). After conditional analysis of each TAGAP SNP, its counterpart remained significantly associated with RA (rs1738074 for rs4709267 P = 0.00001 and rs4709267 for rs1738074 P = 0.00005), suggesting independent effects. CONCLUSION: SNPs in regulatory regions of TAGAP and an intronic SNP (TNFAIP3) are potential susceptibility loci in African Americans. Pairwise LD, haplotype analysis, and SNP conditioning analysis suggest that these 2 SNPs in TAGAP are independent susceptibility alleles. Additional fine-mapping of this gene and functional genomic studies of these SNPs should provide further insight into the role of these genes in RA.
Authors: S T Sherry; M H Ward; M Kholodov; J Baker; L Phan; E M Smigielski; K Sirotkin Journal: Nucleic Acids Res Date: 2001-01-01 Impact factor: 16.971
Authors: A J Mungall; S A Palmer; S K Sims; C A Edwards; J L Ashurst; L Wilming; M C Jones; R Horton; S E Hunt; C E Scott; J G R Gilbert; M E Clamp; G Bethel; S Milne; R Ainscough; J P Almeida; K D Ambrose; T D Andrews; R I S Ashwell; A K Babbage; C L Bagguley; J Bailey; R Banerjee; D J Barker; K F Barlow; K Bates; D M Beare; H Beasley; O Beasley; C P Bird; S Blakey; S Bray-Allen; J Brook; A J Brown; J Y Brown; D C Burford; W Burrill; J Burton; C Carder; N P Carter; J C Chapman; S Y Clark; G Clark; C M Clee; S Clegg; V Cobley; R E Collier; J E Collins; L K Colman; N R Corby; G J Coville; K M Culley; P Dhami; J Davies; M Dunn; M E Earthrowl; A E Ellington; K A Evans; L Faulkner; M D Francis; A Frankish; J Frankland; L French; P Garner; J Garnett; M J R Ghori; L M Gilby; C J Gillson; R J Glithero; D V Grafham; M Grant; S Gribble; C Griffiths; M Griffiths; R Hall; K S Halls; S Hammond; J L Harley; E A Hart; P D Heath; R Heathcott; S J Holmes; P J Howden; K L Howe; G R Howell; E Huckle; S J Humphray; M D Humphries; A R Hunt; C M Johnson; A A Joy; M Kay; S J Keenan; A M Kimberley; A King; G K Laird; C Langford; S Lawlor; D A Leongamornlert; M Leversha; C R Lloyd; D M Lloyd; J E Loveland; J Lovell; S Martin; M Mashreghi-Mohammadi; G L Maslen; L Matthews; O T McCann; S J McLaren; K McLay; A McMurray; M J F Moore; J C Mullikin; D Niblett; T Nickerson; K L Novik; K Oliver; E K Overton-Larty; A Parker; R Patel; A V Pearce; A I Peck; B Phillimore; S Phillips; R W Plumb; K M Porter; Y Ramsey; S A Ranby; C M Rice; M T Ross; S M Searle; H K Sehra; E Sheridan; C D Skuce; S Smith; M Smith; L Spraggon; S L Squares; C A Steward; N Sycamore; G Tamlyn-Hall; J Tester; A J Theaker; D W Thomas; A Thorpe; A Tracey; A Tromans; B Tubby; M Wall; J M Wallis; A P West; S S White; S L Whitehead; H Whittaker; A Wild; D J Willey; T E Wilmer; J M Wood; P W Wray; J C Wyatt; L Young; R M Younger; D R Bentley; A Coulson; R Durbin; T Hubbard; J E Sulston; I Dunham; J Rogers; S Beck Journal: Nature Date: 2003-10-23 Impact factor: 49.962
Authors: Shaun Purcell; Benjamin Neale; Kathe Todd-Brown; Lori Thomas; Manuel A R Ferreira; David Bender; Julian Maller; Pamela Sklar; Paul I W de Bakker; Mark J Daly; Pak C Sham Journal: Am J Hum Genet Date: 2007-07-25 Impact factor: 11.025
Authors: R Chen; E A Stahl; F A S Kurreeman; P K Gregersen; K A Siminovitch; J Worthington; L Padyukov; S Raychaudhuri; R M Plenge Journal: Genes Immun Date: 2011-03-10 Impact factor: 2.676
Authors: Soumya Raychaudhuri; Brian P Thomson; Elaine F Remmers; Stephen Eyre; Anne Hinks; Candace Guiducci; Joseph J Catanese; Gang Xie; Eli A Stahl; Robert Chen; Lars Alfredsson; Christopher I Amos; Kristin G Ardlie; Anne Barton; John Bowes; Noel P Burtt; Monica Chang; Jonathan Coblyn; Karen H Costenbader; Lindsey A Criswell; J Bart A Crusius; Jing Cui; Phillip L De Jager; Bo Ding; Paul Emery; Edward Flynn; Pille Harrison; Lynne J Hocking; Tom W J Huizinga; Daniel L Kastner; Xiayi Ke; Fina A S Kurreeman; Annette T Lee; Xiangdong Liu; Yonghong Li; Paul Martin; Ann W Morgan; Leonid Padyukov; David M Reid; Mark Seielstad; Michael F Seldin; Nancy A Shadick; Sophia Steer; Paul P Tak; Wendy Thomson; Annette H M van der Helm-van Mil; Irene E van der Horst-Bruinsma; Michael E Weinblatt; Anthony G Wilson; Gert Jan Wolbink; Paul Wordsworth; David Altshuler; Elizabeth W Karlson; Rene E M Toes; Niek de Vries; Ann B Begovich; Katherine A Siminovitch; Jane Worthington; Lars Klareskog; Peter K Gregersen; Mark J Daly; Robert M Plenge Journal: Nat Genet Date: 2009-11-08 Impact factor: 38.330
Authors: Rebeca Dieguez-Gonzalez; Manuel Calaza; Eva Perez-Pampin; Alejandro Balsa; Francisco J Blanco; Juan D Cañete; Rafael Caliz; Luis Carreño; Arturo R de la Serna; Benjamin Fernandez-Gutierrez; Ana Maria Ortiz; Gabriel Herrero-Beaumont; Jose L Pablos; Javier Narvaez; Federico Navarro; Jose L Marenco; Juan J Gomez-Reino; Antonio Gonzalez Journal: Arthritis Res Ther Date: 2009-03-17 Impact factor: 5.156
Authors: Gisela Orozco; Anne Hinks; Steve Eyre; Xiayi Ke; Laura J Gibbons; John Bowes; Edward Flynn; Paul Martin; Anthony G Wilson; Deborah E Bax; Ann W Morgan; Paul Emery; Sophia Steer; Lynne Hocking; David M Reid; Paul Wordsworth; Pille Harrison; Wendy Thomson; Anne Barton; Jane Worthington Journal: Hum Mol Genet Date: 2009-05-05 Impact factor: 6.150
Authors: Richard J Reynolds; Altan F Ahmed; Maria I Danila; Laura B Hughes; Peter K Gregersen; Soumya Raychaudhuri; Robert M Plenge; S Louis Bridges Journal: Arthritis Rheumatol Date: 2014-12 Impact factor: 10.995
Authors: Jeffrey D Greenberg; Tanya M Spruill; Ying Shan; George Reed; Joel M Kremer; Jeffrey Potter; Yusuf Yazici; Gbenga Ogedegbe; Leslie R Harrold Journal: Am J Med Date: 2013-12 Impact factor: 4.965
Authors: Changwei Li; Xueli Yang; Jiang He; James E Hixson; Dongfeng Gu; Dabeeru C Rao; Lawrence C Shimmin; Jianfeng Huang; Charles C Gu; Jichun Chen; Jianxin Li; Tanika N Kelly Journal: PLoS One Date: 2014-05-30 Impact factor: 3.240