Pinto Jayant M, Hayes M Geoffrey, Schneider Daniel, Naclerio Robert M, Ober Carole
Section of Otolaryngology-Head and Neck Surgery, Department of Surgery, The University of Chicago, Chicago, Illinois 60637, USA.
Laryngoscope. 2008 Nov;118(11):2067-72. doi: 10.1097/MLG.0b013e3181805147.
OBJECTIVE/HYPOTHESIS: Chronic rhinosinusitis (CRS) is an important public health problem with substantial impact on patient quality of life and health care costs. We hypothesized that genetic variation may be one factor that affects this disease.
Identification of genetic variation underlying susceptibility to CRS using linkage analysis in a founder population.
We studied a religious isolate that practices a communal lifestyle and shares common environmental exposures. Using physical examination, medical interviews, and a review of medical records, we identified eight individuals with CRS of 291 screened. These eight individuals were related to each other in a single 60 member, nine generation pedigree. A genome-wide screen for loci influencing susceptibility to CRS using 1123 genome-wide markers was conducted.
The largest linkage peak (P = .0023; 127.15 cM, equivalent to limit of detection = 2.01) was on chromosome 7q31.1-7q32.1, 7q31 (127.15 cM; 1-limit of detection support region: 115-135 cM) and included the CFTR locus. Genotyping of 38 mutations in the CFTR gene did not reveal variation accounting for this linkage signal.
Understanding the genes involved in CRS may lead to improvements in its diagnosis and treatment. Our results represent the first genome-wide screen for CRS and suggest that a locus on 7q31.1-7q32.1 influences disease susceptibility. This may be the CFTR gene or another nearby locus.
目的/假设：慢性鼻-鼻窦炎（CRS）是一个重要的公共卫生问题，对患者生活质量和医疗费用有重大影响。我们假设基因变异可能是影响该疾病的一个因素。
在一个奠基者人群中使用连锁分析鉴定CRS易感性的基因变异。
我们研究了一个实行集体生活方式且有共同环境暴露的宗教隔离群体。通过体格检查、医学访谈和病历审查，在291名筛查对象中确定了8例CRS患者。这8个人在一个由60名成员组成的九代家系中相互关联。使用1123个全基因组标记对影响CRS易感性的基因座进行全基因组筛查。
最大的连锁峰（P = 0.0023；127.15厘摩，相当于检测限 = 2.01）位于7号染色体7q31.1 - 7q32.1区域，7q31（127.15厘摩；1 - 检测限支持区域：115 - 135厘摩），并包括CFTR基因座。对CFTR基因的38个突变进行基因分型未发现能解释此连锁信号的变异。
了解CRS相关基因可能有助于改善其诊断和治疗。我们的结果代表了首次对CRS进行的全基因组筛查，并表明7q31.1 - 7q32.1区域的一个基因座影响疾病易感性。这可能是CFTR基因或附近的另一个基因座。
