Hensen P, Asadullah K, Windemuth C, Rüschendorf F, Hüffmeier U, Ständer M, Schmitt-Egenolf M, Wienker T F, Reis A, Traupe H
Department of Dermatology, University of Münster, Münster, Germany.
Br J Dermatol. 2003 Aug;149(2):381-5. doi: 10.1046/j.1365-2133.2003.05411.x.
The anti-inflammatory cytokine interleukin (IL)-10 is considered to play a major role in the pathophysiology of psoriasis, which is characterized by an IL-10 deficiency. Systemic administration of IL-10 has been shown to be an effective therapy for psoriasis. The IL-10 promoter region contains a highly polymorphic microsatellite (IL10.G) and in a recent case-control study the IL10.G13 (144 bp) allele was found to be associated with familial early onset psoriasis (type 1 psoriasis) having a susceptible effect.
As it is essential in multifactorial diseases to replicate findings before definite conclusions can be drawn, we decided to perform a follow-up study and to follow a genetic approach analysing allele transmission in families with a positive family history of psoriasis.
We studied 137 nuclear families (trio-design) comprising 456 individuals and genotyped the IL10.G marker. For comparison we also genotyped the microsatellite tn62 as a reference marker of the major psoriasis susceptibility locus on chromosome 6p21 (PSORS1). In the present study allele transmission was evaluated using the family-based association test (FBAT) and GENEHUNTER 2.0 based on the transmission/disequilibrium test.
The G13 allele (144 bp) had a frequency of 24%, was present in 88 families and clearly showed an even transmission (FBAT, P = 0.753). In contrast, allele 3 (IL10.G9) (136 bp) had a frequency of 39%, was present in 110 families and was transmitted in 43 trios and remained untransmitted in 67 trios (FBAT, P = 0.026), thus showing preferential nontransmission. For the HLA-linked tn62-marker we obtained a P-value of 0.00027 for allele 4 in the same study group.
In conclusion, we failed to confirm the susceptible effect of the G13 allele, but provide the first data for a protective effect of allele 3 (IL10.G9) for familial psoriasis. Our results suggest that the IL10.G polymorphism is not a major locus, but acts as a minor locus.
抗炎细胞因子白细胞介素（IL）-10被认为在以IL-10缺乏为特征的银屑病病理生理学中起主要作用。全身给予IL-10已被证明是治疗银屑病的有效方法。IL-10启动子区域包含一个高度多态性的微卫星（IL10.G），在最近的一项病例对照研究中，发现IL10.G13（144bp）等位基因与具有易感性的家族性早发性银屑病（1型银屑病）相关。
由于在得出明确结论之前重复研究结果对于多因素疾病至关重要，我们决定进行一项随访研究，并采用遗传方法分析有银屑病家族史的家庭中的等位基因传递情况。
我们研究了137个核心家庭（三联体设计），共456人，并对IL10.G标记进行基因分型。为了进行比较，我们还对微卫星tn62进行基因分型，作为6号染色体p21上主要银屑病易感基因座（PSORS1）的参考标记。在本研究中，使用基于家系的关联检验（FBAT）和基于传递/不平衡检验的GENEHUNTER 2.0评估等位基因传递情况。
G13等位基因（144bp）的频率为24%，存在于88个家庭中，并且明显显示出均匀传递（FBAT，P = 0.753）。相比之下，等位基因3（IL10.G9）（136bp）的频率为39%，存在于110个家庭中，在43个三联体中传递，在67个三联体中未传递（FBAT，P = 0.026），因此显示出优先不传递。对于与HLA连锁的tn62标记，在同一研究组中，等位基因4的P值为0.00027。
总之，我们未能证实G13等位基因的易感作用，但提供了首个关于等位基因3（IL10.G9）对家族性银屑病具有保护作用的数据。我们的结果表明，IL10.G多态性不是主要基因座，而是作为一个次要基因座起作用。
