WDR36 and P53 Gene Variants and Susceptibility to Primary Open-Angle Glaucoma: Analysis of Gene-Gene Interactions
WDR36 and P53 Gene Variants and Susceptibility to Primary Open-Angle Glaucoma: Analysis of Gene-Gene Interactions
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DOI：
10.1167/iovs.11-7489
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发表时间：
2011-10-01
影响因子：
4.4
通讯作者：
Escribano, Julio
中科院分区：
文献类型：
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作者：
Blanco-Marchite, Cristina;Sanchez-Sanchez, Francisco;Escribano, Julio
目的.探讨WDR 36和P53序列变异在POAG易感性中的作用。方法。作者在268名无关的西班牙患者（POAG 1）和380名性别、年龄和种族匹配的对照受试者中进行了病例对照遗传关联研究。通过直接DNA测序或变性高效液相色谱法筛选WDR 36序列变异。分别采用单核苷酸多态性（SNP）基因分型和PCR方法检测P53基因多态性p.R72P和c.97- 147 ins 16 bp。在211例患者的第二个样本和合并病例（n = 479）中重新分析了阳性SNP和单倍型相关性。作者发现了近50种WDR 36序列变异，其中约三分之二是罕见的，三分之一是多态性。大约一半的变体是新的。8例患者（2.9%）携带对照组未发现的罕见突变（P = 0.001）。六个标签SNP预计将在三个常见的单倍型结构。单倍型H2与该疾病一致相关（在合并病例中P = 0.0024）。根据显性模型，含有P53 p.R72P SNP的等位基因P的基因型轻微增加青光眼风险。与不同WDR 36基因型相关的青光眼易感性与P53 RP风险基因型的结合也显著增加，表明存在遗传相互作用。例如，在两位点基因型H2/RP中，H2双倍型对POAG 1和合并病例的OR估计值上升了约1.6倍。罕见的WDR 36变异和P53 p.R72P多态性在西班牙患者中表现为中度青光眼危险因素。作者提供的证据表明，在POAG易感性中，WDR 36和P53变异体之间存在遗传相互作用，尽管这一发现必须在其他人群中得到证实。（Invest Ophthalmol维斯科学。2011;52：8467-8478）DOI：10.1167/iovs.11-7489
PURPOSE. To investigate the role of WDR36 and P53 sequence variations in POAG susceptibility.METHODS. The authors performed a case-control genetic association study in 268 unrelated Spanish patients (POAG1) and 380 control subjects matched for sex, age, and ethnicity. WDR36 sequence variations were screened by either direct DNA sequencing or denaturing high-performance liquid chromatography. P53 polymorphisms p.R72P and c.97-147ins16bp were analyzed by single-nucleotide polymorphism (SNP) genotyping and PCR, respectively. Positive SNP and haplotype associations were reanalyzed in a second sample of 211 patients and in combined cases (n = 479).RESULTS. The authors identified almost 50 WDR36 sequence variations, of which approximately two-thirds were rare and one-third were polymorphisms. Approximately half the variants were novel. Eight patients (2.9%) carried rare mutations that were not identified in the control group (P = 0.001). Six Tag SNPs were expected to be structured in three common haplotypes. Haplotype H2 was consistently associated with the disease (P = 0.0024 in combined cases). According to a dominant model, genotypes containing allele P of the P53 p.R72P SNP slightly increased glaucoma risk. Glaucoma susceptibility associated with different WDR36 genotypes also increased significantly in combination with the P53 RP risk genotype, indicating the existence of a genetic interaction. For instance, the OR of the H2 diplotype estimated for POAG1 and combined cases rose approximately 1.6 times in the two-locus genotype H2/RP.CONCLUSIONS. Rare WDR36 variants and the P53 p.R72P polymorphism behaved as moderate glaucoma risk factors in Spanish patients. The authors provide evidence for a genetic interaction between WDR36 and P53 variants in POAG susceptibility, although this finding must be confirmed in other populations. (Invest Ophthalmol Vis Sci. 2011;52: 8467-8478) DOI:10.1167/iovs.11-7489