The evidence for association of ATP2B2 polymorphisms with autism in Chinese Han population.
The evidence for association of ATP2B2 polymorphisms with autism in Chinese Han population.
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ATP2B2 多态性与中国汉族人群自闭症相关的证据
DOI：
10.1371/journal.pone.0061021
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Wang L
中科院分区：
文献类型：
--
作者：
Yang W;Liu J;Zheng F;Jia M;Zhao L;Lu T;Ruan Y;Zhang J;Yue W;Zhang D;Wang L
自闭症是一种神经发育障碍，遗传率很高。位于人类染色体3p25.3上的ATP2B2编码质膜钙转运ATPase 2，该酶负责将胞浆中的钙离子排入胞外。最近的研究报告了来自自闭症遗传资源交易所(AGRE)和意大利的样本中ATP2B2与自闭症的关联。在本研究中，我们调查了ATP2B2基因多态性是否与中国汉族人群的自闭症相关。我们对427例汉族自闭症患者进行了ATP2B2基因5个单核苷酸多态(外显子rs35678、内含子rs241509、rs3774180、rs3774179和rs2278556)与孤独症的家系关联研究。使用Sequenom基因分型平台对所有SNP进行基因分型。使用基于家族的关联检验(FBAT)程序进行SNPs关联检验和单倍型分析。本研究证明在加性模型(T>；C，Z = 2.482，p = 0.013)下，rs3774179的T等位基因优先传递给患病后代。而rs3774179的C等位基因在加性模型和显性模型下分别表现为父母向患病儿童传递不足(Z = −2.482，p = 0.013；Z = −2.591，p = 0.0096)。单倍型分析显示，三种单倍型与自闭症显著相关。单倍型C-C(rs3774180-rs3774179)在特定单倍型和全局单倍型Fbat中均表现出显著的亲子传递不足(Z = −2.037，p = 0.042；全球p = 0.03)。对于rs3774179和rs2278556构建的单倍型，C-A可能是一种保护性单倍型(Z = −2.206，p = 0.027；Global p = 0.04)，而T-A表现出从父母向患病后代的过度遗传(Z = 2.143，p = 0.032)。在使用排列法获得经验p值后，这些结果仍然具有重要意义。本研究提示ATP2B2基因可能在中国汉族人群孤独症的发病机制中起一定作用。
Autism is a neurodevelopmental disorder with a high estimated heritability. ATP2B2, located on human chromosome 3p25.3, encodes the plasma membrane calcium-transporting ATPase 2 which extrudes Ca2+ from cytosol into extracellular space. Recent studies reported association between ATP2B2 and autism in samples from Autism Genetic Resource Exchange (AGRE) and Italy. In this study, we investigated whether ATP2B2 polymorphisms were associated with autism in Chinese Han population. We performed a family based association study between five SNPs (rs35678 in exon, rs241509, rs3774180, rs3774179, and rs2278556 in introns) in ATP2B2 and autism in 427 autism trios of Han Chinese descent. All SNPs were genotyped using the Sequenom genotyping platform. The family-based association test (FBAT) program was used to perform association test for SNPs and haplotype analyses. This study demonstrated a preferential transmission of T allele of rs3774179 to affected offsprings under an additive model (T>C, Z = 2.482, p = 0.013). While C allele of rs3774179 showed an undertransmission from parents to affected children under an additive and a dominant model, respectively (Z = −2.482, p = 0.013; Z = −2.591, p = 0.0096). Haplotype analyses revealed that three haplotypes were significantly associated with autism. The haplotype C-C (rs3774180–rs3774179) showed a significant undertransmission from parents to affected offsprings both in specific and global haplotype FBAT (Z = −2.037, p = 0.042; Global p = 0.03). As for the haplotype constructed by rs3774179 and rs2278556, C-A might be a protective haplotype (Z = −2.206, p = 0.027; Global p = 0.04), while T-A demonstrated an excess transmission from parents to affected offsprings (Z = 2.143, p = 0.032). These results were still significant after using the permutation method to obtain empirical p values. Our research suggested that ATP2B2 might play a role in the etiology of autism in Chinese Han population.
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