AJHG：GWAS方法鉴定出子宫肌瘤相关的遗传突变FAS基因

    子宫肌瘤是妇女常见的一种骨盆肿瘤，其在美国是妇女子宫切除的主要原因之一，来自布莱根妇女医院的研究者利用全基因组方法，首次发现了白人妇女子宫肌瘤的遗传风险等位基因，相关研究发现于10月4日刊登在了国际杂志The American Journal of Human Genetics上，这项研究或为子宫肌瘤的疗法提供思路和帮助。

    这项研究中，研究者对7000名白人妇女的遗传数据进行了分析，并且检测了其和子宫肌瘤相关的遗传突变，包括检测了编码脂肪酸合酶FAS的基因FASN等系列基因。

    有研究表明，相比正常子宫肌肉层样品，子宫肌瘤样品中FAS蛋白的表达量是前者的三倍，在其它类型的肿瘤中，研究者也发现了FAS蛋白的过量表达，而且其是肿瘤细胞生存所必须的。

    研究者Morton表示，我们的研究发现为开发子宫肌瘤患者的个体化疗法带来了帮助，遗传风险因子的识别更加快了开发的进程。子宫肌瘤或导致异常的阴道出血、不育等疾病，因此加速开发其新型疗法对于患者至关重要。

与GWAS相关的拓展阅读：

• Science：人类疾病全基因组关联分析（GWAS）获进展
• Mol Psychi：GWAS证实精神分裂症遗传易感位点
• Nat Gene：采用GWAS方法发现中风相关的遗传基因HDAC9
• PLoS Genetics：GWAS方法鉴定出与帕金森氏症相关两新位点
• GWAS技术发现麻风和精神分裂症易感基因
更多信息请点击：有关GWAS更多资讯

    编译自：Genetic Risk for Uterine Fibroids Identified

doi:10.1016/j.ajhg.2012.08.009
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Genome-wide Linkage and Association Analyses Implicate FASN in Predisposition to Uterine Leiomyomata

Stacey L. Eggert1, Karen L. Huyck4, Priya Somasundaram2, Raghava Kavalla2, Elizabeth A. Stewart5, Ake T. Lu6, Jodie N. Painter7, Grant W. Montgomery7, Sarah E. Medland7, Dale R. Nyholt7, Susan A. Treloar7, 8, Krina T. Zondervan9, Andrew C. Heath10, Pamela A.F. Madden10, Lynda Rose11, Julie E. Buring11, 12, Paul M. Ridker11, 12, Daniel I. Chasman11, 12, Nicholas G. Martin7, Rita M. Cantor6 and Cynthia C. Morton2

Uterine leiomyomata (UL), the most prevalent pelvic tumors in women of reproductive age, pose a major public health problem given their high frequency, associated morbidities, and most common indication for hysterectomies. A genetic component to UL predisposition is supported by analyses of ethnic predisposition, twin studies, and familial aggregation. A genome-wide SNP linkage panel was genotyped and analyzed in 261 white UL-affected sister-pair families from the Finding Genes for Fibroids study. Two significant linkage regions were detected in 10p11 (LOD = 4.15) and 3p21 (LOD = 3.73), and five additional linkage regions were identified with LOD scores > 2.00 in 2q37, 5p13, 11p15, 12q14, and 17q25. Genome-wide association studies were performed in two independent cohorts of white women, and a meta-analysis was conducted. One SNP (rs4247357) was identified with a p value (p = 3.05 108) that reached genome-wide significance (odds ratio = 1.299). The candidate SNP is under a linkage peak and in a block of linkage disequilibrium in 17q25.3, which spans fatty acid synthase (FASN), coiled-coil-domain-containing 57 (CCDC57), and solute-carrier family 16, member 3 (SLC16A3). By tissue microarray immunohistochemistry, we found elevated (3-fold) FAS levels in UL-affected tissue compared to matched myometrial tissue. FAS transcripts and/or protein levels are upregulated in various neoplasms and implicated in tumor cell survival. FASN represents the initial UL risk allele identified in white women by a genome-wide, unbiased approach and opens a path to management and potential therapeutic intervention.