Matrix metalloproteinase-2 promoter variability in psoriasis
Matrix metalloproteinase-2 promoter variability in psoriasis
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DOI：
10.1007/s00403-009-0947-5
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发表时间：
2009-07-01
影响因子：
3
通讯作者：
Vasku, Anna
中科院分区：
文献类型：
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作者：
Vasku, Vladimir;Vasku, Julie Bienertova;Vasku, Anna
观察到基质金属蛋白酶-2 的表达在银屑病中显着上调。本研究的目的是将 MMP-2 启动子基因中的 DNA 多态性变异与银屑病和/或与银屑病和共病遗传相关的银屑病表型联系起来。在总共 582 名捷克白人个体中（386 名银屑病患者和 196 名年龄和性别分布相似的对照者，无个人或家族慢性皮肤病史），通过 PCR 方法检测到 4 个 MMP-2 启动子多态性（-1575G/A、-1306C/T、-790T/G 和 -735C/T）。观察到 -790 MMP-2 多态性的 GG 基因型与银屑病显着相关（Pcorr = 0.04）。虽然相关 GG(-1575)CC(-1306)TT(-790) MMP-2 启动子基因型的频率没有观察到显着的病例对照差异，但发现在有银屑病家族史（近亲和远亲）、糖尿病家族史和个人过敏史的患者中，该基因型的频率显着较低（2/11 vs. 55/32，GGCCTT 的比值比 (OR) 0.11， 95% 置信区间 0.02-0.50，Pcorr = 0.01)。与仅有糖尿病家族史的银屑病患者相比，具有糖尿病、银屑病和过敏阳性记忆数据的银屑病患者之间也观察到显着差异（2/11 vs. 38/31，P = 0.009，Pcorr = 0.04；对于具有 GGCCTT 基因型和家族史的银屑病患者，OR 0.15，95% CI = 0.03-0.72牛皮癣、糖尿病和个人过敏史）。总之，与无银屑病家族史、糖尿病和个人过敏史的银屑病患者相比，MMP-2基因启动子中相关GGCCTT基因型的出现频率较低（2/11 vs. 68/57，P = 0.007，Pcorr = 0.04；对于有家族史的银屑病患者，OR = 0.15，95% CI = 0.03-0.72有牛皮癣、糖尿病和过敏史）。根据我们的结果，我们建议位于 16q 银屑病易感区（银屑病易感性 8，PSORS8）的 MMP-2 应被视为特定亚组患者银屑病的基因调节剂。将来，类似的遗传特征可能有助于银屑病遗传易感性的数据组装，并可能导致基于在银屑病患者中检测到的经过时间证明的个体药物遗传学方面的治疗改进。
The expression of matrix metalloproteinase-2 was observed to be significantly upregulated in psoriasis. The aim of this study was to associate the DNA polymorphic variants in MMP-2 promoter gene with psoriasis and/or with psoriasis phenotypes related to psoriasis and comorbid heredity. In the total of 582 Czech Caucasian individuals (386 patients with psoriasis and 196 controls of similar age and sex distribution without personal or family history of chronic disease of the skin), four MMP-2 promoter polymorphisms (-1575G/A, -1306C/T, -790T/G and -735C/T) were detected by PCR methods. A significant association of GG genotype of -790 MMP-2 polymorphism with psoriasis was observed (Pcorr = 0.04). Although no significant case-control differences in frequency of associated GG(-1575)CC(-1306)TT(-790) MMP-2 promoter genotype were observed, the genotype was found to be significantly less frequent in patients with family history of psoriasis (close as well as distant), family history of diabetes and personal history of allergy (2/11 vs. 55/32, odds ratio (OR) for GGCCTT 0.11, 95% confidential interval 0.02-0.50, Pcorr = 0.01). The significant difference between psoriatic patients with positive anamnestic data on diabetes, psoriasis and allergy compared with psoriatic patients that have only positive family history of diabetes was also observed (2/11 vs. 38/31, P = 0.009, Pcorr = 0.04; OR 0.15, 95% CI = 0.03-0.72 for psoriatic patients with GGCCTT genotype and family history of psoriasis, diabetes and personal history of allergy). To conclude, the associated GGCCTT genotype in the promoter of MMP-2 gene was less frequent in patients with positive family history of psoriasis, diabetes and personal history of allergy compared with psoriatic patients without them (2/11 vs. 68/57, P = 0.007, Pcorr = 0.04; OR = 0.15, 95% CI = 0.03-0.72 for psoriatic patients with family history of psoriasis and diabetes and with allergy). Based on our results, we suggest that the MMP-2 located in the psoriasis susceptibility region on 16q (psoriasis susceptibility 8, PSORS8) should be considered as a gene modulator of psoriasis in specific subgroups of patients. In the future, similar genetic characteristics could contribute to the data assembly of genetic predisposition to psoriasis and could lead to therapy improvement based on time-proved individual pharmacogenetic aspects detected in psoriasis patients.