Hall Andrew J, Quinnell Rupert J, Raiko Andrew, Lagog Moses, Siba Peter, Morroll Shaun, Falcone Franco H
Immune Modulation Research Group, School of Pharmacy, University of Nottingham, Nottingham NG7 2RD, United Kingdom.
Infect Genet Evol. 2007 Dec;7(6):743-7. doi: 10.1016/j.meegid.2007.07.010. Epub 2007 Jul 28.
Human chitotriosidase (CHIT1) is a chitinolytic enzyme with suggested anti-fungal properties. Previous studies have suggested that chitotriosidase may also protect individuals against filarial nematode infections and malaria. A mutant allele, which renders chitotriosidase unstable and enzymatically inactive, is found at a frequency of >20% in Caucasians and other populations. This allele is found at much lower frequency in parts of West Africa where malarial and intestinal helminth infections are endemic. Here, we investigate whether there is a significant association between chitotriosidase genotype and the intensity of hookworm infection in 693 individuals from five villages in Papua New Guinea. Individuals were genotyped for chitotriosidase using a PCR-based assay. There was no association between CHIT1 genotype and the intensity of hookworm infection as determined by faecal egg counts. The frequency of the mutant allele was 0.251, very similar to that found in non-endemic countries. The extent of geographical variation in allele frequencies across worldwide populations was not high (F(st)=0.11), and does not provide evidence for directional selection at this locus between different geographical areas. We conclude that the CHIT1 genotype does not play a crucial role in protection against hookworm infection. This does not correlate with a previous study that linked the mutant CHIT1 genotype to filariasis susceptibility. The possible reasons for this discrepancy are discussed.
人几丁质酶(CHIT1)是一种具有抗真菌特性的几丁质分解酶。先前的研究表明,几丁质酶可能还能保护个体免受丝虫线虫感染和疟疾侵害。在高加索人和其他人群中,发现一种使几丁质酶不稳定且无酶活性的突变等位基因,其频率>20%。在疟疾和肠道蠕虫感染流行的西非部分地区,该等位基因的频率要低得多。在此,我们调查了来自巴布亚新几内亚五个村庄的693名个体的几丁质酶基因型与钩虫感染强度之间是否存在显著关联。使用基于聚合酶链反应的检测方法对个体的几丁质酶进行基因分型。根据粪便虫卵计数确定,CHIT1基因型与钩虫感染强度之间没有关联。突变等位基因的频率为0.251,与在非流行国家发现的频率非常相似。全球人群中等位基因频率的地理变异程度不高(Fst=0.11),并且没有提供该位点在不同地理区域之间存在定向选择的证据。我们得出结论,CHIT1基因型在预防钩虫感染方面不发挥关键作用。这与之前将突变的CHIT1基因型与丝虫病易感性联系起来的研究不相关。讨论了这种差异的可能原因。