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白细胞介素-10基因多态性影响非霍奇金淋巴瘤的临床病程。

Interleukin-10 gene polymorphisms influence the clinical course of non-Hodgkin's lymphoma.

作者信息

Bogunia-Kubik K, Mazur G, Wróbel T, Kuliczkowski K, Lange A

机构信息

Department of Clinical Immunology, L. Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.

出版信息

Tissue Antigens. 2008 Feb;71(2):146-50. doi: 10.1111/j.1399-0039.2007.00984.x.

DOI:10.1111/j.1399-0039.2007.00984.x
PMID:18201362
Abstract

The pathophysiology of Non-Hodgkin's lymphoma (NHL) is still unknown and clinical course is very unpredictable. Many cytokines, including interleukin-10 (IL-10), play a role in the perpetuation of this disease. The IL-10-producing capability has been found to be influenced by the IL-10 gene promoter polymorphisms. The aim of the present study was to assess whether any of IL-10 (-1082 A/G, -819 C/T and -592 A/C) genotypes prevails in Polish patients with NHL and whether IL-10 promoter polymorphisms may be associated with less or more favourable course of the disease. IL-10 gene promoter polymorphisms were assessed in 105 individuals, including 55 NHL patients and 50 ethically matched controls. The frequency of the IL-10 low-producing -1082 AA homozygous genotype was significantly higher in patients with aggressive NHL as compared with patients with indolent forms of the disease (0.57 vs 0.28, P < 0.05) and controls [0.57 vs 0.32, odds ratio (OR) = 2.69, P < 0.05]. Also, the presence of the ACC genotype was more frequently detected among patients with more aggressive disease than in those with indolent forms (0.74 vs 0.47, P < 0.05) and healthy controls (0.74 vs 0.42, OR = 3.69, P < 0.05). In multivariate analyses, the AA homozygosity (OR = 6.33, P < 0.05) and ACC genotype (OR = 3.57, P = 0.05) appeared as independent risk factors of more aggressive manifestation of NHL in addition to the elevated lactate dehydrogenase 480 level. Although no direct association was found between IL-10 promoter polymorphisms and NHL, IL-10 (-1082) AA homozygosity and IL-10 ACC genotype were found to be associated with unfavourable prognosis in patients with NHL.

摘要

非霍奇金淋巴瘤(NHL)的病理生理学仍不清楚,临床病程极难预测。许多细胞因子,包括白细胞介素-10(IL-10),在该疾病的持续发展中起作用。已发现产生IL-10的能力受IL-10基因启动子多态性影响。本研究的目的是评估IL-10(-1082 A/G、-819 C/T和-592 A/C)的任何基因型在波兰NHL患者中是否占优势,以及IL-10启动子多态性是否可能与疾病的病程较有利或较不利相关。对105名个体进行了IL-10基因启动子多态性评估,其中包括55名NHL患者和50名伦理匹配的对照。与惰性形式疾病的患者相比,侵袭性NHL患者中IL-10低产生型-1082 AA纯合基因型的频率显著更高(0.57对0.28,P<0.05),与对照相比也是如此[0.57对0.32,优势比(OR)=2.69,P<0.05]。此外,与惰性形式疾病的患者相比,侵袭性更强的疾病患者中ACC基因型的检出频率更高(0.74对0.47,P<0.05),与健康对照相比也是如此(0.74对0.42,OR=3.69,P<0.05)。在多变量分析中,除乳酸脱氢酶水平升高至480外,AA纯合性(OR=6.33,P<0.05)和ACC基因型(OR=3.57,P=0.0(5))是NHL更具侵袭性表现的独立危险因素。虽然未发现IL-10启动子多态性与NHL之间存在直接关联,但发现IL-10(-1082)AA纯合性和IL-10 ACC基因型与NHL患者的不良预后相关。

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