Sequence, haplotype, and association analysis of ADRβ2 in a multiethnic asthma case-control study
Sequence, haplotype, and association analysis of ADRβ2 in a multiethnic asthma case-control study
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DOI：
10.1164/rccm.200509-1405oc
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发表时间：
2006-11-15
影响因子：
24.7
通讯作者：
Bleecker, Eugene R.
中科院分区：
文献类型：
--
作者：
Hawkins, Gregory A.;Tantisira, Kelan;Bleecker, Eugene R.
理由：基因变异、单倍型结构和连锁不平衡的综合评价对于理解β(2)-肾上腺素能受体基因(ADR β 2)对不同种族哮喘患者的疾病易感性、肺功能和治疗反应的功能具有重要意义。目的：鉴定白人和非裔美国人受试者中的ADR β 2多态性和单倍型结构，并测试基因型和单倍型与哮喘的关联表型。方法：对来自 429 名白人和 240 名非裔美国人的 669 名个体的 ADR beta 2 的 5.3 kb 区域进行了重新测序。在白人（338 名患者和 326 名对照受试者）和非裔美国人（222 名患者和 299 名对照受试者）中对总共 12 个多态性（代表最佳单倍型标记集）进行了基因分型。 结果：总共鉴定了 49 个多态性，其中 21 个是新的； 31 个多态性（频率 > 0.03）用于鉴定 24 个单倍型（频率 > 0.01）并评估连锁不平衡。在非裔美国人中观察到单核仁多态性与比率 (FEV1/FVC)(2) +79 (p < 0.05) 的关联。在非洲裔美国人中也观察到 (FEV1/FVC)(2) 的显着单倍型关联。结论：除了 +46 (Gly(16)Arg) 之外，还有其他遗传变异对于确定哮喘表型也很重要。这些数据表明，ADR β 2 3'非翻译区中多聚 C 重复序列 (+1269) 的长度可能会影响肺功能，并且对于描述 P 激动剂反应的变化可能很重要，尤其是在非裔美国人中。
Rationale: The comprehensive evaluation of gene variation, haplotype structure, and linkage disequilibrium is important in understanding the function Of beta(2)-adrenergic receptor gene (ADR beta 2) on disease susceptibility, pulmonary function, and therapeutic responses in different ethnic groups with asthma.Objectives: To identify ADR beta 2 polymorphisms and haplotype structure in white and African American subjects and to test for genotype and haplotype association with asthma phenotypes.Methods:A 5.3-kb region of ADR beta 2 was resequenced in 669 individuals from 429 whites and 240 African Americans. A total of 12 polymorphisms, representing an optimal haplotype tagging set, were genotyped in whites (338 patients and 326 control subjects) and African Americans (222 patients and 299 control subjects).Results: A total of 49 polymorphisms were identified, 21 of which are novel; 31 polymorphisms (frequency > 0.03) were used to identify 24 haplotypes (frequency > 0.01) and assess linkage disequilibrium. Association with ratio (FEV1/FVC)(2) for single-nucleoticle polymorphism +79 (p < 0.05) was observed in African Americans. Significant haplotype association for (FEV1/FVC)(2) was also observed in African Americans.Conclusions: There are additional genetic variants besides +46 (Gly(16)Arg) that are important in determining asthma phenotypes. These data suggest that the length of a poly-C repeat (+1269) in the 3' untranslated region of ADR beta 2 may influence lung function, and may be important in delineating variation in P-agonist responses, especially in African Americans.