Tsai Yuhjung J, Choudhry Shweta, Kho Jennifer, Beckman Kenneth, Tsai Hui-Ju, Navarro Daniel, Matallana Henry, Castro Richard A, Lilly Craig M, Nazario Sylvette, Rodriguez-Santana Jose R, Casal Jesus, Torres Alfonso, Salas Jorge, Chapela Rocio, Watson H George, Meade Kelley, Avila Pedro C, Rodriguez-Cintron William, LeNoir Michael, Burchard Esteban González
University of California, San Francisco, San Francisco, CA 94143-2911, USA.
J Allergy Clin Immunol. 2006 Dec;118(6):1242-8. doi: 10.1016/j.jaci.2006.07.045. Epub 2006 Sep 26.
The prostanoid DP receptor (PTGDR) gene on chromosome 14q22.1 has been identified as an asthma susceptibility gene. A haplotype with decreased transcription factor binding and transcription efficiency was associated with decreased asthma susceptibility in African American and white subjects. The significance of PTGDR gene variants in asthma has yet to be determined in Latinos, the largest US minority population, nor has the association been replicated in other populations.
To determine the role of PTGDR gene variants in asthma susceptibility and asthma-related traits among the Mexican, Puerto Rican, and African American populations.
We determined whether single nucleotide polymorphisms (SNPs) and haplotypes in PTGDR were associated with asthma and asthma-related traits by family-based and cross-sectional cohort analyses in 336 Puerto Rican and 273 Mexican asthmatic trios and by case-control analysis among African American subjects with asthma and healthy controls (n = 352).
We identified 13 SNPs in the PTGDR gene, and 6 were further analyzed. There was no significant association between PTGDR variants and asthma by family-based or case-control analyses. SNPs -441C and -197C and haplotype TTT showed marginal association with asthma-related traits in Mexican subjects. SNP -441 genotype TT (P = .05) and haplotype TTT (P = .02) were associated with increased IgE levels in African Americans.
We conclude that the PTGDR gene is not a significant risk factor for asthma among Puerto Ricans, Mexicans, or African Americans.
Asthma candidate genes provide insights to pathophysiology and potentially new therapeutic targets, although the PTGDR gene was not found to be a significant risk factor for asthma in 3 populations.
位于14q22.1染色体上的前列腺素DP受体（PTGDR）基因已被确定为哮喘易感基因。一种转录因子结合和转录效率降低的单倍型与非裔美国人和白人受试者哮喘易感性降低有关。PTGDR基因变异在哮喘中的意义尚未在拉丁裔（美国最大的少数族裔群体）中确定，且该关联也未在其他人群中得到重复验证。
确定PTGDR基因变异在墨西哥人、波多黎各人及非裔美国人哮喘易感性和哮喘相关特征中的作用。
我们通过对336个波多黎各人和273个墨西哥人哮喘三联体进行基于家系和横断面队列分析，以及对非裔美国哮喘患者和健康对照（n = 352）进行病例对照分析，来确定PTGDR中的单核苷酸多态性（SNP）和单倍型是否与哮喘及哮喘相关特征相关。
我们在PTGDR基因中鉴定出13个SNP，其中6个进行了进一步分析。基于家系或病例对照分析，PTGDR变异与哮喘之间均无显著关联。SNP -441C和 -197C以及单倍型TTT在墨西哥受试者中与哮喘相关特征呈边缘性关联。SNP -441基因型TT（P = .05）和单倍型TTT（P = .02）与非裔美国人IgE水平升高相关。
我们得出结论，PTGDR基因在波多黎各人、墨西哥人或非裔美国人中并非哮喘的重要危险因素。
哮喘候选基因有助于了解病理生理学并可能提供新的治疗靶点，尽管在3个群体中未发现PTGDR基因是哮喘的重要危险因素。
