哥斯达黎加哮喘患儿家庭肺功能的全基因组连锁分析。
Genome-wide linkage analysis of pulmonary function in families of children with asthma in Costa Rica.
作者信息
Hersh Craig P, Soto-Quirós Manuel E, Avila Lydiana, Lake Stephen L, Liang Catherine, Fournier Eduardo, Spesny Mitzi, Sylvia Jody S, Lazarus Ross, Hudson Thomas, Verner Andrei, Klanderman Barbara J, Freimer Nelson B, Silverman Edwin K, Celedón Juan C
机构信息
Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, 181 Longwood Avenue, Boston, MA 02115, USA.
出版信息
Thorax. 2007 Mar;62(3):224-30. doi: 10.1136/thx.2006.067934. Epub 2006 Nov 10.
BACKGROUND
Although asthma is highly prevalent among certain Hispanic subgroups, genetic determinants of asthma and asthma-related traits have not been conclusively identified in Hispanic populations. A study was undertaken to identify genomic regions containing susceptibility loci for pulmonary function and bronchodilator responsiveness (BDR) in Costa Ricans.
METHODS
Eight extended pedigrees were ascertained through schoolchildren with asthma in the Central Valley of Costa Rica. Short tandem repeat (STR) markers were genotyped throughout the genome at an average spacing of 8.2 cM. Multipoint variance component linkage analyses of forced expiratory volume in 1 second (FEV(1)) and FEV(1)/ forced vital capacity (FVC; both pre-bronchodilator and post-bronchodilator) and BDR were performed in these eight families (pre-bronchodilator spirometry, n = 640; post-bronchodilator spirometry and BDR, n = 624). Nine additional STR markers were genotyped on chromosome 7. Secondary analyses were repeated after stratification by cigarette smoking.
RESULTS
Among all subjects, the highest logarithm of the odds of linkage (LOD) score for FEV(1) (post-bronchodilator) was found on chromosome 7q34-35 (LOD = 2.45, including the additional markers). The highest LOD scores for FEV(1)/FVC (pre-bronchodilator) and BDR were found on chromosomes 2q (LOD = 1.53) and 9p (LOD = 1.53), respectively. Among former and current smokers there was near-significant evidence of linkage to FEV(1)/FVC (post-bronchodilator) on chromosome 5p (LOD = 3.27) and suggestive evidence of linkage to FEV(1) on chromosomes 3q (pre-bronchodilator, LOD = 2.74) and 4q (post-bronchodilator, LOD = 2.66).
CONCLUSIONS
In eight families of children with asthma in Costa Rica, there is suggestive evidence of linkage to FEV(1) on chromosome 7q34-35. In these families, FEV(1)/FVC may be influenced by an interaction between cigarette smoking and a locus (loci) on chromosome 5p.
背景
尽管哮喘在某些西班牙裔亚组中高度流行，但西班牙裔人群中哮喘及哮喘相关性状的遗传决定因素尚未得到最终确定。开展了一项研究，以确定哥斯达黎加人中包含肺功能和支气管扩张剂反应性（BDR）易感基因座的基因组区域。
方法
通过哥斯达黎加中央山谷患有哮喘的学童确定了8个扩展家系。在整个基因组中对短串联重复（STR）标记进行基因分型，平均间距为8.2厘摩。对这8个家系进行了1秒用力呼气量（FEV(1)）、FEV(1)/用力肺活量（FVC；支气管扩张剂使用前和使用后）以及BDR的多点方差成分连锁分析（支气管扩张剂使用前肺量计检查，n = 640；支气管扩张剂使用后肺量计检查和BDR，n = 624）。在7号染色体上对另外9个STR标记进行了基因分型。按吸烟情况分层后重复进行了二次分析。
结果
在所有受试者中，FEV(1)（支气管扩张剂使用后）的最高连锁对数优势（LOD）分数在7q34 - 35染色体上被发现（LOD = 2.45，包括另外的标记）。FEV(1)/FVC（支气管扩张剂使用前）和BDR的最高LOD分数分别在2q染色体（LOD = 1.53）和9p染色体（LOD = 1.53）上被发现。在曾经吸烟和当前吸烟的人群中，有接近显著的证据表明5p染色体上与FEV(1)/FVC（支气管扩张剂使用后）存在连锁（LOD = 3.27），以及有提示性证据表明3q染色体（支气管扩张剂使用前，LOD = 2.74）和4q染色体（支气管扩张剂使用后，LOD = 2.66）上与FEV(1)存在连锁。
结论
在哥斯达黎加8个患有哮喘儿童的家系中，有提示性证据表明7q34 - 35染色体上与FEV(1)存在连锁。在这些家系中，FEV(1)/FVC可能受吸烟与5p染色体上一个或多个基因座之间的相互作用影响。
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