BACKGROUND: Asthma is a complex disease characterized by a high prevalence of allergic diathesis and the almost ubiquitous presence of upper airway disease (eg, rhinitis). Previously, we observed linkage of asthma among Afro-Caribbean families to markers in chromosome 12q, which contains a number of genes encoding for products closely related to allergic airway inflammation and disease. OBJECTIVE: To identify susceptibility loci in chromosome 12q contributing to the genetics of upper and lower airway diseases and to expand the region to include genes encoding IFN-gamma (IFNG ) and one of the signal transducers and activators of transcription (STAT6 ), we conducted further linkage studies among 33 multiplex families. METHODS: We characterized 528 subjects from Barbados for asthma; 82% were characterized for allergic rhinitis. Two-point and multipoint linkage analysis of 22 microsatellite markers (spanning approximately 79 centimorgan) was performed. RESULTS: Affected sib-pair analysis revealed significant evidence for linkage to asthma over approximately 30 cM (P <.05 to.002), with the best evidence for linkage at a CA repeat polymorphism in the first intron of IFNG in 12q21.1 (P =.002). Evidence of linkage to allergic rhinitis was observed in the same region (D12S313, P = 0.006, and IFNGCA, P =.01, respectively). Multipoint linkage analysis also provided evidence for linkage to asthma, with the best nonparametric linkage analysis score at D12S326 (nonparametric linkage score = 3.8, P =.0008). Modest evidence for linkage to allergic rhinitis was observed next to D12S326 at D12S1052 (P =.036). CONCLUSIONS: Our findings suggest that (1) one or more loci in the chromosome 12q13. 12-q23.3 region are contributing to the expression of the clinical phenotype asthma and the strongest evidence for linkage is in a region near the gene encoding IFNG and (2) a susceptibility locus for both asthma and allergic rhinitis maps to this region.
BACKGROUND:Asthma is a complex disease characterized by a high prevalence of allergic diathesis and the almost ubiquitous presence of upper airway disease (eg, rhinitis). Previously, we observed linkage of asthma among Afro-Caribbean families to markers in chromosome 12q, which contains a number of genes encoding for products closely related to allergic airway inflammation and disease. OBJECTIVE: To identify susceptibility loci in chromosome 12q contributing to the genetics of upper and lower airway diseases and to expand the region to include genes encoding IFN-gamma (IFNG ) and one of the signal transducers and activators of transcription (STAT6 ), we conducted further linkage studies among 33 multiplex families. METHODS: We characterized 528 subjects from Barbados for asthma; 82% were characterized for allergic rhinitis. Two-point and multipoint linkage analysis of 22 microsatellite markers (spanning approximately 79 centimorgan) was performed. RESULTS: Affected sib-pair analysis revealed significant evidence for linkage to asthma over approximately 30 cM (P <.05 to.002), with the best evidence for linkage at a CA repeat polymorphism in the first intron of IFNG in 12q21.1 (P =.002). Evidence of linkage to allergic rhinitis was observed in the same region (D12S313, P = 0.006, and IFNGCA, P =.01, respectively). Multipoint linkage analysis also provided evidence for linkage to asthma, with the best nonparametric linkage analysis score at D12S326 (nonparametric linkage score = 3.8, P =.0008). Modest evidence for linkage to allergic rhinitis was observed next to D12S326 at D12S1052 (P =.036). CONCLUSIONS: Our findings suggest that (1) one or more loci in the chromosome 12q13. 12-q23.3 region are contributing to the expression of the clinical phenotype asthma and the strongest evidence for linkage is in a region near the gene encoding IFNG and (2) a susceptibility locus for both asthma and allergic rhinitis maps to this region.
Authors: Swapan K Nath; Ana I Quintero-Del-Rio; Jeff Kilpatrick; Lourdes Feo; Maria Ballesteros; John B Harley Journal: Am J Hum Genet Date: 2003-12-04 Impact factor: 11.025
Authors: Juan C Celedón; Manuel E Soto-Quiros; Lydiana Avila; Stephen L Lake; Catherine Liang; Eduardo Fournier; Mitzi Spesny; Craig P Hersh; Jody S Sylvia; Thomas J Hudson; Andrei Verner; Barbara J Klanderman; Nelson B Freimer; Edwin K Silverman; Scott T Weiss Journal: Hum Genet Date: 2006-09-26 Impact factor: 4.132
Authors: Nathaniel Weathington; Michael E O'Brien; Josiah Radder; Thomas C Whisenant; Eugene R Bleecker; William W Busse; Serpil C Erzurum; Benjamin Gaston; Annette T Hastie; Nizar N Jarjour; Deborah A Meyers; Jadranka Milosevic; Wendy C Moore; John R Tedrow; John B Trudeau; Hesper P Wong; Wei Wu; Naftali Kaminski; Sally E Wenzel; Brian D Modena Journal: Am J Respir Crit Care Med Date: 2019-10-01 Impact factor: 21.405
Authors: Dagan A Loisel; Zheng Tan; Christopher J Tisler; Michael D Evans; Ronald E Gangnon; Daniel J Jackson; James E Gern; Robert F Lemanske; Carole Ober Journal: J Allergy Clin Immunol Date: 2011-07-27 Impact factor: 10.793