Choi E H, Zimmerman P A, Foster C B, Zhu S, Kumaraswami V, Nutman T B, Chanock S J
Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Genes Immun. 2001 Aug;2(5):248-53. doi: 10.1038/sj.gene.6363767.
A pilot study was conducted to determine if host genetic factors influence susceptibility and outcomes in human filariasis. Using the candidate gene approach, a well-characterized population in South India was studied using common polymorphisms in six genes (CHIT1, MPO, NRAMP, CYBA, NCF2, and MBL2). A total of 216 individuals from South India were genotyped; 67 normal (N), 63 asymptomatic microfilaria positive (MF+), 50 with chronic lymphatic dysfunction/elephantiasis (CP), and 36 tropical pulmonary eosinophilia (TPE). An association was observed between the HH variant CHIT1 genotype, which correlates with decreased activity and levels of chitotriosidase and susceptibility to filarial infection (MF+ and CP; P = 0.013). The heterozygosity of CHIT1 gene was over-represented in the normal individuals (P = 0.034). The XX genotype of the promoter region in MBL2 was associated with susceptibility to filariasis (P = 0.0093). Since analysis for MBL-sufficient vs insufficient haplotypes was not informative, it is possible the MBL2 promoter association results from linkage disequilibrium with neighboring loci. We have identified two polymorphisms, CHIT1 and MBL2 that are associated with susceptibility to human filarial infection, findings that merit further follow-up in a larger study.
开展了一项初步研究，以确定宿主遗传因素是否会影响人类丝虫病的易感性和预后。采用候选基因法，利用六个基因（几丁质酶1、髓过氧化物酶、天然抗性相关巨噬细胞蛋白、细胞色素b-245α链、中性粒细胞胞浆因子2和甘露聚糖结合凝集素2）的常见多态性，对印度南部一个特征明确的人群进行了研究。对来自印度南部的216名个体进行了基因分型；67名正常个体（N）、63名无症状微丝蚴阳性个体（MF+）、50名患有慢性淋巴功能障碍/象皮病的个体（CP）和36名热带肺嗜酸性粒细胞增多症患者（TPE）。观察到几丁质酶1基因的HH变异基因型与几丁质三糖苷酶活性和水平降低以及丝虫感染易感性（MF+和CP；P = 0.013）之间存在关联。几丁质酶1基因的杂合性在正常个体中过度表达（P = 0.034）。甘露聚糖结合凝集素2启动子区域的XX基因型与丝虫病易感性相关（P = 0.0093）。由于对甘露聚糖结合凝集素充足与不足单倍型的分析无信息价值，甘露聚糖结合凝集素2启动子关联可能是由于与相邻基因座的连锁不平衡导致的。我们鉴定出了两个与人类丝虫感染易感性相关的多态性，即几丁质酶1和甘露聚糖结合凝集素2，这些发现值得在更大规模的研究中进一步跟进。
