Hawkins Gregory A, Amelung Pamela J, Smith Richard S, Jongepier Hajo, Howard Timothy D, Koppelman Gerard H, Meyers Deborah A, Bleecker Eugene R, Postma Dirkje S
Wake Forest University School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157, USA.
DNA Seq. 2004 Jun;15(3):167-73. doi: 10.1080/10425170410001704517.
The glucocorticoid receptor (GR) gene (NR3C1) maps to 5q31, a region genetically linked to asthma. In this study, NR3C1 exons 1A, 1B, and exons 1C to 9 (alpha and beta) were sequenced in a screening panel of asthmatics and unaffected controls from US Caucasian, African American, US Hispanic, and Dutch Caucasian populations to identify polymorphisms for genetic association studies. Eight polymorphisms were identified in exon 1A, but none were located in putative transcription regulatory sites. Thirty-four polymorphisms were identified in exons 1B to 9 (alpha and beta), 17 of which were novel. Eight coding polymorphisms were identified (4 non-synonymous). One novel mutation (Ala229Thr) was identified in a Hispanic individual. Linkage disequilibrium (LD) was strongest between polymorphisms spanning intron 2 to exon 9beta. This data shows the variability of NR3C1 polymorphism frequencies between racial groups and confirms that NR3C1 non-synonymous coding polymorphisms are generally rare in mild/moderate asthmatics and unaffected controls.
糖皮质激素受体(GR)基因(NR3C1)定位于5q31,该区域在基因上与哮喘相关。在本研究中,对来自美国白种人、非裔美国人、美国西班牙裔和荷兰白种人群的哮喘患者及未受影响对照的筛查样本进行了NR3C1基因外显子1A、1B以及外显子1C至9(α和β)的测序,以鉴定用于基因关联研究的多态性。在外显子1A中鉴定出8个多态性,但均不在假定的转录调控位点。在外显子1B至9(α和β)中鉴定出34个多态性,其中17个是新发现的。鉴定出8个编码多态性(4个非同义突变)。在一名西班牙裔个体中鉴定出一个新的突变(Ala229Thr)。跨越内含子2至外显子9β的多态性之间的连锁不平衡(LD)最强。该数据显示了不同种族群体间NR3C1多态性频率的变异性,并证实NR3C1非同义编码多态性在轻度/中度哮喘患者和未受影响对照中通常很少见。