Challa Pratap, Schmidt Silke, Liu Yutao, Qin Xuejun, Vann Robin R, Gonzalez Pedro, Allingham R Rand, Hauser Michael A
Department of Ophthalmology, Duke University Eye Center, Durham, NC 27710, USA.
Mol Vis. 2008 Jan 29;14:146-9.
To identify if recently described LOXL1 (lysyl oxidase-like 1) polymorphisms are associated with pseudoexfoliation glaucoma (XFG) in a United States (U.S.) Caucasian patient population.
Individuals with XFG were identified using standard clinical examination techniques. TaqMan allelic discrimination assays were used to genotype 13 single nucleotide polymorphisms (SNPs) that tag LOXL1 in Caucasian individuals. The coding region of exon 1 that includes the previously associated SNP, rs1048661, was sequenced. Allele and genotype frequencies were compared between cases and unrelated controls.
Fifty affected individuals and 235 control individuals were recruited into this study. We replicated the previously reported association of three SNPs (rs1048661, rs2165241, and rs3825942) in our independent XFG population (single SNP p-values were 0.001-0.02). The risk alleles at these three and several other intragenic SNPs are part of an extended XFG-associated LOXL1 haplotype with a frequency of 32.0% in XFG patients and 21.6% in controls.
We have performed an analysis of LOXL1 and XFG in a United States patient population and have confirmed the strong association previously reported for Icelandic and Swedish samples. However, due to the high frequency of risk alleles in non-XFG individuals, this association should not form the basis of a diagnostic test for XFG. It is likely that additional genetic or environmental factors modulate the penetrance of LOXL1 susceptibility alleles.
确定最近描述的赖氨酰氧化酶样1（LOXL1）基因多态性是否与美国白种人患者群体中的剥脱性青光眼（XFG）相关。
采用标准临床检查技术识别XFG患者。使用TaqMan等位基因鉴别分析对13个标记白种人个体中LOXL1的单核苷酸多态性（SNP）进行基因分型。对包含先前相关SNP（rs1048661）的外显子1编码区进行测序。比较病例组与无关对照组的等位基因和基因型频率。
本研究招募了50名患病个体和235名对照个体。我们在独立的XFG群体中重复了先前报道的三个SNP（rs1048661、rs2165241和rs3825942）的关联（单个SNP的p值为0.001 - 0.02）。这三个以及其他几个基因内SNP的风险等位基因是一个与XFG相关的扩展LOXL1单倍型的一部分，在XFG患者中的频率为32.0%，在对照组中为21.6%。
我们对美国患者群体中的LOXL1和XFG进行了分析，并证实了先前冰岛和瑞典样本报道的强关联。然而，由于非XFG个体中风险等位基因的高频率，这种关联不应作为XFG诊断测试的基础。可能还有其他遗传或环境因素调节LOXL1易感等位基因的外显率。
