中国汉族人群腋臭易感基因的相关性研究

Axillary osmidrosis(AO) is characterized by an unpleasant odor, profuse sweating, and in some instances, staining of clothes that may socially and psychologically impair affected individuals. The exact aetiology of AO remains obscure. It has been reported that about 80% patients with AO have family history, however very few articles have aimed to illuminate the genetic profiles of AO. Recently, the ApoD has been identified as an axillary odorant binding protein, and ApoD expression is regulated by the AR. Besides, there is strong evidence suggesting that a functional ABCC11 allele, rs17822931, is essential for the secretion of apocrine sweat glands. However, the association study of these genes and AO is far from perfect, and very few studies have focused on AO susceptibility gene in the Chinese Han population. To systematic investigate the association between the ABCC11,AR and ApoD gene variation and susceptibility to AO in Chinese Population, we plan to sequence all the exons, exon-intron boundaries as well as promoter region of these three genes in 48 patients of and 48 normal controls. Then we will genotype potential associated variants in larger independent samples and construct risk haplotypes to confirm the associations. Furthermore, a series of functional studies will be conducted including immunohistochemistry, Real-Time quantitative RT-PCR, Western blot, luciferase assay and so on to validate the plausible susceptibility variations. This study will not only advance our understanding of the genetic basis of AO but also provide new insights into the disease prediction and prevention.

腋臭是一种常见疾病，表现为腋窝顶泌汗腺分泌物排出皮肤表面所产生的特殊刺鼻臭味，严重影响患者日常生活和人际交往，其确切病因尚不清楚。本病与遗传关系密切，约80%患者有家族史，然而其遗传学研究甚少。研究表明ApoD作为臭味分子的载体，是腋臭发生分子机制中的核心蛋白，AR则可调节ApoD 表达；而ABCC11基因rs17822931位点目前被认为是与顶泌汗腺分泌功能密切相关的位点。但是目前对这些基因与腋臭相关性的系统研究尚不完善，国内对于腋臭易感基因研究尚属空白。因此，我们拟采用直接测序的策略结合关联分析检测汉族人腋臭的ABCC11、AR和ApoD基因多态性，明确其是否与腋臭相关，并采用免疫组化、实时定量PCR、Western-blot等方法进行系列功能研究，以期鉴定出与腋臭发病相关的功能性变异。这是首次在中国汉族人腋臭患者中展开大规模的遗传学研究，为阐明腋臭的发病机制和治疗提供分子遗传学基础。

腋臭是一种常见疾病，表现为腋窝顶泌汗腺分泌物排出皮肤表面所产生的特殊刺鼻臭味，严重影响患者日常生活和人际交往。其确切病因尚不明确，目前认为与遗传关系密切。近来有研究表明ApoD 作为臭味分子的载体，是腋臭发生分子机制中的核心蛋白，AR 则可调节ApoD 表达，位于染色体16q12.1 区域的ABCC11 基因上的rs17822931 位点则被认为是与顶泌汗腺分泌功能密切相关的位点之一。然而这些基因与腋臭相关性的系统研究尚不完善，国内对于腋臭易感基因研究尚属空白。因此，我们利用候选基因的方法，选择了ABCC11(rs17822931), ApoD(rs5952), LIPC(rs1800588), BUD13-ZNF259 (rs964184), LDLR(rs1003723), SCNN1G(rs7200183), EGF(rs4444903), EGFR(rs1050171), GGT1(rs4820599, rs8135987) 9个基因的10个SNP位点作为候选基因位点，利用SNPshot进行基因分型，分别在收集到的两个独立的汉族腋臭人群（93病例vs 95 对照以及81病例vs106对照）中进行了相关性分析。结果证实ABCC11基因rs17822931位点等位基因频率在腋臭患者和正常对照间存在显著性差异(Pcombined=1.42E-21, OR=83.94, 95%CI= 83.03-84.85)，进一步进行基因型和表型的相关性分析发现携带rs17822931-G等位基因的患者与湿性叮咛(P= 2.40E-05)、阳性家族史(P=1.04E-02)以及发病年龄早(P=3.81E-02)均存在显著相关性。此外，我们的研究结果还首次发现BUD13-ZNF259区域的rs964184位点与在中国汉族人群腋臭的发病存在显著相关性(Pcombined=5.12E-03, OR=0.51, 95%CI=0.05-0.98)。. 这是首次在中国汉族人腋臭患者中展开大规模的遗传学研究，为进一步阐明腋臭的发病机制、风险预测和新的治疗靶标奠定理论基础。项目实施期间，先后在分别发于 Oncol Rep（IF:2.486）和 Oncotarget（IF5.008）发表2篇SCI论文，Scientific Report（IF5.228）修回1篇SCI论文；协助培养硕士生2名