The association between mannan-binding lectin gene polymorphism and clinical leprosy: New insight into an old paradigm
The association between mannan-binding lectin gene polymorphism and clinical leprosy: New insight into an old paradigm
复制标题
DOI：
10.1086/521627
复制
发表时间：
2007-11-01
影响因子：
6.4
通讯作者：
Kun, Juergen F. J.
中科院分区：
文献类型：
--
作者：
de Messias-Reason, Iara J.;Boldt, Angelica B. W.;Kun, Juergen F. J.
背景。甘露聚糖结合凝集素（MBL）是一种天然免疫的可溶性蛋白，已知在病原体识别和清除中起作用。十多年来，人们提出MBL缺乏可能对细胞内病原体（如麻风分枝杆菌）有保护作用。对来自巴西南部的264例麻风病患者和214例健康对照者进行了MBL2基因启动子和外显子1区域多态性的聚合酶链反应和测序分析。mbl2基因多态性在患者中的分布与对照组有显著差异，与结核样患者相比，麻风病患者中与循环MBL低表达相关的单倍型/基因型的频率降低（单倍型的比值比[OR]为0.56[95%可信区间{CI}， 0.33-0.93] [P = 0.020]；基因型的比值比[OR]为0.31 [95% CI, 0.13-0.71] [P = 0.004]）。LYPA单倍型与麻风病本身的易感性（OR, 2.25 [95% CI, 1.31-3.88] [P = 0.003]）、发展为麻风型（OR, 2.2 [95% CI, 1.21-4.05] [P = 0.008]）和边缘型（OR, 2.98 [95% CI, 1.29-6.87] [P = 0.008]）相关。这些结果表明，mbl2基因多态性在麻风病本身的易感性和疾病的临床进展中发挥作用。
Background. Mannan-binding lectin (MBL), a soluble protein of innate immunity, is known to play a role in pathogen recognition and clearance. For more than a decade, it has been proposed that MBL deficiency may be protective against intracellular pathogens, such as Mycobacterium leprae.Methods. The polymorphisms at the promoter and exon 1 regions of the MBL2 gene were assessed by polymerase chain reaction and sequencing performed on 264 patients with leprosy and 214 matched healthy control subjects from southern Brazil.Results. The distribution of MBL2-gene polymorphisms in patients was significantly different from that in controls, with a decreased frequency of haplotypes/genotypes associated with low expression of circulating MBL in lepromatous patients when compared with tuberculoid patients (odds ratio [OR] for haplotypes, 0.56 [95% confidence interval {CI}, 0.33-0.93] [P = .020]; OR for genotypes, 0.31 [95% CI, 0.13-0.71] [P = .004]). The LYPA haplotype was associated with susceptibility to leprosy per se (OR, 2.25 [95% CI, 1.31-3.88] [P = .003]) and to progression to the lepromatous (OR, 2.2 [95% CI, 1.21-4.05] [P = .008]) and borderline (OR, 2.98 [95% CI, 1.29-6.87] [P = .008]) forms of the disease.Conclusions. These results suggest that MBL2-gene polymorphisms play a role in susceptibility to leprosy per se and in the clinical progression of the disease.