Lee Pauline, Waalen Jill, Crain Karen, Smargon Aaron, Beutler Ernest
The Scripps Research Institute, Department of Molecular and Experimental Medicine, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Blood Cells Mol Dis. 2007 Nov-Dec;39(3):353-60. doi: 10.1016/j.bcmd.2007.06.013. Epub 2007 Aug 10.
A common polymorphism in the chitotriosidase gene (CHIT1) exists in which a 24 bp duplication in exon 10 results in aberrant splicing and deletion of 87 nucleotides. In this study, the gene frequency was found to be 0.56 (n=2054) in subjects of Asian ancestry, 0.17 (n=984) in subjects of European ancestry and 0.07 (n=536) in subjects of African ancestry. Notably, the median enzyme activity in wild-type subjects (TT) was much higher in subjects of European ancestry (2.69 mU/ml, n=202 subjects), than subjects of African (2.57 mU/ml, n=230 subjects) (P<0.0001) and Asian ancestry (0.86 mU/ml, n=114 subjects) (P<0.0001). The question of why chitotriosidase deficiency exists at such a high frequency is a challenging one. We postulated that if there was a selective advantage for chitotriosidase deficiency then there would be polymorphisms that would be associated with reduced enzyme activity independent of the 24 bp duplication. We found that the G102S and the A442G polymorphisms found occurring in subjects of all ancestries were not significantly associated with a reduction of enzyme activity. In contrast, the G354R (P<0.0001) and the A442V (P=0.0013) polymorphisms occurring predominantly in subjects of African ancestry were significantly associated with reduced chitotriosidase activity. We also investigated the possibility that chitotriosidase deficiency was associated with tuberculosis or with atopy, including allergic rhinitis, contact dermatitis, food or drug allergies and asthma.
几丁质酶基因（CHIT1）存在一种常见的多态性，其中第10外显子24bp的重复导致异常剪接并缺失87个核苷酸。在本研究中，亚洲血统受试者的基因频率为0.56（n = 2054），欧洲血统受试者为0.17（n = 984），非洲血统受试者为0.07（n = 536）。值得注意的是，野生型受试者（TT）的平均酶活性在欧洲血统受试者（2.69 mU/ml，n = 202名受试者）中比非洲血统受试者（2.57 mU/ml，n = 230名受试者）（P < 0.0001）和亚洲血统受试者（0.86 mU/ml，n = 114名受试者）（P < 0.0001）高得多。几丁质酶缺乏为何以如此高的频率存在是一个具有挑战性的问题。我们推测，如果几丁质酶缺乏具有选择性优势，那么就会存在与酶活性降低相关的多态性，而与24bp重复无关。我们发现，在所有血统受试者中出现的G102S和A442G多态性与酶活性降低无显著关联。相比之下，主要出现在非洲血统受试者中的G354R（P < 0.0001）和A442V（P = 0.0013）多态性与几丁质酶活性降低显著相关。我们还研究了几丁质酶缺乏与结核病或特应性疾病（包括过敏性鼻炎、接触性皮炎、食物或药物过敏以及哮喘）相关的可能性。
