Significant linkage to airway responsiveness on chromosome 12q24 in families of children with asthma in Costa Rica
Significant linkage to airway responsiveness on chromosome 12q24 in families of children with asthma in Costa Rica
复制标题
DOI：
10.1007/s00439-006-0255-5
复制
发表时间：
2007-01-01
期刊：
影响因子：
5.3
通讯作者：
Weiss, Scott T.
中科院分区：
文献类型：
--
作者：
Celedon, Juan C.;Soto-Quiros, Manuel E.;Weiss, Scott T.
尽管在美国和拉丁美洲的某些西语裔群体中，哮喘是一个主要的公共卫生问题，但只有一次哮喘的基因组扫描包括了西语裔个人。由于样本量小，该研究在检测拉美裔参与者中与哮喘及其中间表型的联系方面的统计能力有限。为了在居住在哥斯达黎加中央山谷的与世隔绝的西班牙裔人群中识别包含哮喘易感基因和呼吸道反应性的基因组区域，我们对8个哥斯达黎加哮喘儿童大家系成员进行了哮喘(n=638)和呼吸道反应性(n=488)的全基因组连锁分析。非参数多点连锁分析采用NPL-Pair等位基因共享统计法，多点连锁分析采用方差成分模型作为定量表型。排除既往吸烟者和现在吸烟者的表型数据后，重复所有连锁分析。染色体12Q显示了一些与哮喘有关的证据，特别是在不吸烟的人中(P<；0.01)。在非吸烟者中，有证据表明12q24.31(146 cM的LOD=2.33)与呼吸道反应性有关。在对染色体12q上另外18个短串联重复序列标记进行基因分型后，在染色体12q24.31上发现了与呼吸道反应性连锁的显著证据(LOD=3.79，位于144 cM)，对于观察到的连锁高峰(142-147 cM)，1.5-LOD单位支持区间相对较窄。我们的结果表明，染色体12q24.31包含一个或多个影响哥斯达黎加人哮喘关键中间表型(呼吸道反应性)的基因座。
Although asthma is a major public health problem in certain Hispanic subgroups in the United States and Latin America, only one genome scan for asthma has included Hispanic individuals. Because of small sample size, that study had limited statistical power to detect linkage to asthma and its intermediate phenotypes in Hispanic participants. To identify genomic regions that contain susceptibility genes for asthma and airway responsiveness in an isolated Hispanic population living in the Central Valley of Costa Rica, we conducted a genome-wide linkage analysis of asthma (n = 638) and airway responsiveness (n = 488) in members of eight large pedigrees of Costa Rican children with asthma. Nonparametric multipoint linkage analysis of asthma was conducted by the NPL-PAIR allele-sharing statistic, and variance component models were used for the multipoint linkage analysis of airway responsiveness as a quantitative phenotype. All linkage analyses were repeated after exclusion of the phenotypic data of former and current smokers. Chromosome 12q showed some evidence of linkage to asthma, particularly in nonsmokers (P < 0.01). Among nonsmokers, there was suggestive evidence of linkage to airway responsiveness on chromosome 12q24.31 (LOD = 2.33 at 146 cM). After genotyping 18 additional short-tandem repeat markers on chromosome 12q, there was significant evidence of linkage to airway responsiveness on chromosome 12q24.31 (LOD = 3.79 at 144 cM), with a relatively narrow 1.5-LOD unit support interval for the observed linkage peak (142-147 cM). Our results suggest that chromosome 12q24.31 contains a locus (or loci) that influence a critical intermediate phenotype of asthma (airway responsiveness) in Costa Ricans.