Brasch-Andersen C, Haagerup A, Børglum A D, Vestbo J, Kruse T A
J Med Genet. 2006 Mar;43(3):e10. doi: 10.1136/jmg.2005.035519.
Allergic diseases such as asthma and rhinitis have closely related phenotypes and often occur with atopy. They show strong familial and intra-individual clustering, suggesting overlapping disease aetiology. Various loci and candidate genes have been suggested to underlie allergy. Many or all are still inconclusive. Following genome-wide scans on multiple phenotypes, we previously suggested that chromosome 3q13.12-q21.2 harbours an allergy locus.
To identify candidate loci in the Danish population, two additional independent sets of sib-pair families were fine-scale mapped in candidate regions showing maximum likelihood scores (MLS) > or =1.5 in the genome-wide scans.
Twenty eight microsatellite markers in a denser map on chromosome 3q were analysed in 236 allergy sib-pair families including 125 sib pairs with rhinitis. We report significant evidence for linkage to chromosome 3q13.31 for rhinitis (MLS 5.55, identity by descent (IBD) 63.9%) and atopy (increased specific immunoglobulin E) (MLS 3.71, IBD 61.7%). We obtained an MLS of 5.1 (IBD 67.3%) at 3q13.31 when sib pairs with both rhinitis and atopy were analysed.
This study reports the first statistically significant evidence for a genetic susceptibility locus for rhinitis and to our knowledge shows the most significant evidence to date of linkage for any allergy phenotype.
哮喘和鼻炎等过敏性疾病具有密切相关的表型，且常与特应性同时出现。它们呈现出强烈的家族聚集性和个体内聚集性，提示病因重叠。已提出多个位点和候选基因与过敏相关。但许多或所有结果仍无定论。在对多种表型进行全基因组扫描后，我们之前曾提出3号染色体q13.12 - q21.2区域存在一个过敏位点。
为了在丹麦人群中确定候选位点，对另外两组独立的同胞对家族进行精细定位，这些家族来自全基因组扫描中最大似然分数（MLS）≥1.5的候选区域。
在236个过敏同胞对家族（包括125个患有鼻炎的同胞对）中分析了3号染色体q上更密集图谱中的28个微卫星标记。我们报告了与3号染色体q13.31区域存在连锁的显著证据，针对鼻炎（MLS 5.55，同源等位基因一致性（IBD）63.9%）和特应性（特异性免疫球蛋白E升高）（MLS 3.71，IBD 61.7%）。当分析同时患有鼻炎和特应性的同胞对时，在3q13.31区域获得了5.1（IBD 67.3%）的MLS。
本研究首次报告了鼻炎遗传易感性位点的统计学显著证据，据我们所知，这也是迄今为止任何过敏表型连锁的最显著证据。
