Shin H D, Park B L, Kim L H, Kim J-S, Kim J-W
Department of Genetic Epidemiology, SNP Genetics, Inc., Seoul, Korea.
Allergy. 2005 Sep;60(9):1146-51. doi: 10.1111/j.1398-9995.2005.00839.x.
The genetic background of atopic dermatitis (AD) is not clearly understood. Interleukin (IL)-10 is a powerful Th-2 cell cytokine produced by lymphoid cells that exerts its function by inhibiting macrophage/monocyte and T-cell lymphocyte replication and secretion of inflammatory cytokines [IL-1, tumour necrosis factor-alpha (TNFA), IL-6, IL-8 and IL-12].
In an effort to discover additional polymorphism(s) in genes whose variant(s) have been implicated in total immunoglobulin E (IgE) level in AD patients, we scrutinized the single nucleotide polymorphisms (SNPs) in the IL10 gene as a potent candidate for contributing to the level of IgE in serum.
We recruited 334 AD patients and assayed their serum total IgE levels using the LIPA-200 system. Four SNPs in the IL10 gene were genotyped using the single-base extension (SBE) method. Logistic regression analyses were performed with single polymorphisms and haplotypes (ht) to determine their association with the level of serum total IgE.
Genetic association analysis of total serum IgE in AD patients revealed that one of the IL10 ht, IL10-ht2, was associated with decreased serum total IgE in gene dose-dependent manner (P = 0.02-0.001).
It was predicted that the inhibition of innate immunity by increased IL-10 production in IL10-ht2-bearing individuals might be associated with decreased total serum IgE levels among AD patients. The greater effects of IL10 ht on decreased total serum IgE levels suggest that the effect of IL-10 polymorphism might be the result of a combined genotype (ht) rather than single polymorphisms.
特应性皮炎（AD）的遗传背景尚不清楚。白细胞介素（IL）-10是一种由淋巴细胞产生的强大的Th2细胞细胞因子，它通过抑制巨噬细胞/单核细胞以及T细胞淋巴细胞的复制和炎性细胞因子[IL-1、肿瘤坏死因子-α（TNFA）、IL-6、IL-8和IL-12]的分泌来发挥其功能。
为了发现其变异与AD患者总免疫球蛋白E（IgE）水平相关的基因中的其他多态性，我们仔细研究了IL10基因中的单核苷酸多态性（SNP），将其作为影响血清IgE水平的有力候选基因。
我们招募了334例AD患者，并使用LIPA-200系统检测他们血清中的总IgE水平。采用单碱基延伸（SBE）法对IL10基因中的4个SNP进行基因分型。对单核苷酸多态性和单倍型（ht）进行逻辑回归分析，以确定它们与血清总IgE水平的关联。
AD患者血清总IgE的遗传关联分析显示，IL10单倍型之一IL10-ht2与血清总IgE降低呈基因剂量依赖性相关（P = 0.02 - 0.001）。
据推测，携带IL10-ht2的个体中IL-10产生增加对先天免疫的抑制可能与AD患者血清总IgE水平降低有关。IL10单倍型对血清总IgE水平降低的影响更大，这表明IL-10多态性的影响可能是组合基因型（单倍型）而非单核苷酸多态性的结果。
