2012年9月17日 電 /生物谷BIOON/ --由安徽醫(yī)科大學(xué)和BGI領(lǐng)導(dǎo)的一中國研究小組最新證實甲羥戊酸激酶基因（MVK）遺傳突變和彌漫性淺表性光化性汗孔角化癥（DSAP）之間有密切聯(lián)系,。這項研究發(fā)現(xiàn)為揭示DSAP遺傳發(fā)病機制邁進了一大步,，有助于開發(fā)分子診斷和治療技術(shù),。研究結(jié)果發(fā)表在Nature Genetics雜志上,。
DSAP是一種罕見的非腫瘤類型,、非傳染性的皮膚疾病,，會導(dǎo)致患者胳膊和腿皮膚干燥,，發(fā)癢病變,。持續(xù)日曬是導(dǎo)致患DSAP的一個危險因素。雖然DSAP是一種慢性疾病,，它是可以治療的,，但一直以來這種疾病不能得到完全治愈。
在這項研究中,，研究人員對屬于同一個有DSAP疾病史家庭的兩例受影響和一例未受影響的個體進行基因組測序,。通過變體分析和數(shù)據(jù)過濾，研究人員猜測MVK基因是唯一一個與DSAP發(fā)病相關(guān)的候選基因,。
MVK編碼蛋白質(zhì)甲羥戊酸激酶,，甲羥戊酸激酶是一個重要的甲羥戊酸途徑的酶，通過提供必需的生物活性分子多種細(xì)胞過程,。MVK的表達(dá)對角質(zhì)形成細(xì)胞生物活性的影響,，研究人員表示，MVK能調(diào)節(jié)鈣誘導(dǎo)的角質(zhì)形成細(xì)胞的分化,，同時MVK的表達(dá)可以防止因UVA引起的角質(zhì)形成細(xì)胞的凋亡,。
該項目的高級科學(xué)家Tao Jiang說，我們的研究DSAP的發(fā)病機制提供了新的見解,，并確定MVK突變是基因診斷和臨床治療該類疾病的最佳的候選靶標(biāo),。
這項研究的通訊作者安徽醫(yī)科大學(xué)Xuejun Zhang說，基因組測序是一種有效的方法來鑒定單基因遺傳性疾病的疾病基因,，這項研究不僅標(biāo)志著中國在世界上尋找單基因遺傳病的致病基因處于最先進的水平,，用死也為揭示DSAP的發(fā)病機制、進行疾病風(fēng)險預(yù)測,、藥物開發(fā),、臨床診斷和治療提供了科學(xué)依據(jù)。（生物谷：Bioon.com）
doi:10.1038/ng.2409
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Exome sequencing identifies MVK mutations in disseminated superficial actinic porokeratosis.
Sheng-Quan Zhang, Tao Jiang, Min Li, Xin Zhang, Yun-Qing Ren, Sheng-Cai Wei, Liang-Dan Sun, Hui Cheng, Yang Li, Xian-Yong Yin, Zheng-Mao Hu, Zhen-Ying Wang, Yuan Liu, Bi-Rong Guo, Hua-Yang Tang, Xian-Fa Tang, Yan-Tao Ding, Jian-Bo Wang, Ping Li, Bao-Yu Wu, Wen Wang, Xiang-Feng Yuan, Jun-Sheng Hou, Wei-Wei Ha, Wen-Ju Wang, Yu-Juan Zhai, Jing Wang, Fang-Fang Qian, Fu-Sheng Zhou, Gang Chen, Xian-Bo Zuo, Xiao-Dong Zheng, Yu-Jun Sheng, Jin-Ping Gao, Bo Liang, Pan Li, Jun Zhu, Feng-Li Xiao, Pei-Guang Wang, Yong Cui, Hui Li, Sheng-Xiu Liu, Min Gao, Xing Fan, Song-Ke Shen, Ming Zeng, Guang-Qing Sun, Yu Xu, Jing-Chu Hu, Ting-Ting He, Ying-Rui Li, Huan-Ming Yang, Jian Wang, Zhong-Yi Yu, Hui-Feng Zhang, Xin Hu, Ke Yang, Jie Wang, Shi-Xiang Zhao, You-Wen Zhou, Jian-Jun Liu, Wei-Dong Du, Li Zhang, Kun Xia, Sen Yang, Jun Wang, Xue-Jun Zhang.
Disseminated superficial actinic porokeratosis (DSAP) is an autosomal dominantly inherited epidermal keratinization disorder whose etiology remains unclear. We performed exome sequencing in one unaffected and two affected individuals from a DSAP family. The mevalonate kinase gene (MVK) emerged as the only candidate gene located in previously defined linkage regions after filtering against existing SNP databases, eight HapMap exomes and 1000 Genomes Project data and taking into consideration the functional implications of the mutations. Sanger sequencing in 57 individuals with familial DSAP and 25 individuals with sporadic DSAP identified MVK mutations in 33% and 16% of these individuals (cases), respectively. All 14 MVK mutations identified in our study were absent in 676 individuals without DSAP. Our functional studies in cultured primary keratinocytes suggest that MVK has a role in regulating calcium-induced keratinocyte differentiation and could protect keratinocytes from apoptosis induced by type A ultraviolet radiation. Our results should help advance the understanding of DSAP pathogenesis.
