Fondazione G,B, Bietti-IRCCS, Via Livenza 3, 00198 Rome, Italy.
BMC Ophthalmol. 2014 Apr 16;14:52. doi: 10.1186/1471-2415-14-52.
Single nucleotide polymorphisms (SNPs) within the LOXL1 gene are associated with pseudoesfoliation syndrome and pseudoesfoliation glaucoma. The aim of our study is to investigate a potential involvement of LOXL1 gene in the pathogenesis of pigment dispersion syndrome (PDS) and pigmentary glaucoma (PG).
A cohort of Caucasian origin of 84 unrelated and clinically well-characterised patients with PDS/PG and 200 control subjects were included in the study. Genomic DNA from whole blood was extracted and the coding and regulatory regions of LOXL1 gene were risequenced in both patients and controls to identify unknown sequence variations. Genotype and haplotype analysis were performed with UNPHASED software. The expression levels of LOXL1 were determined on c-DNA from peripheral blood lymphocytes by quantitative real-time RT-PCR.
A significant allele association was detected for SNP rs2304722 within the fifth intron of LOXL1 (Odds ratio (OR = 2.43, p-value = 3,05e-2). Haplotype analysis revealed the existence of risk and protective haplotypes associated with PG-PDS (OR = 3.35; p-value = 1.00e-5 and OR = 3.35; p-value = 1.00e-4, respectively). Expression analysis suggests that associated haplotypes can regulate the expression level LOXL1.
Haplotypes of LOXL1 are associated with PG-PDS independently from rs1048661, leading to a differential expression of the transcript.
LOXL1 基因中的单核苷酸多态性（SNPs）与假性剥脱综合征和假性剥脱性青光眼有关。我们研究的目的是探讨 LOXL1 基因在色素播散综合征（PDS）和色素性青光眼（PG）发病机制中的潜在作用。
本研究纳入了 84 名无血缘关系且临床特征明确的白种人 PDS/PG 患者和 200 名对照。从全血中提取基因组 DNA，并对患者和对照者的 LOXL1 基因编码区和调控区进行测序，以鉴定未知的序列变异。采用 UNPHASED 软件进行基因型和单倍型分析。通过实时定量 RT-PCR 测定外周血淋巴细胞 c-DNA 中 LOXL1 的表达水平。
在 LOXL1 的第五内含子中发现了 SNP rs2304722 的显著等位基因关联（优势比（OR）=2.43，p 值=3.05e-2）。单倍型分析显示，与 PG-PDS 相关的风险和保护单倍型存在（OR=3.35;p 值=1.00e-5 和 OR=3.35;p 值=1.00e-4）。表达分析表明，相关单倍型可以调节 LOXL1 的表达水平。
LOXL1 的单倍型与 rs1048661 无关，与 PG-PDS 相关，导致转录本的表达水平存在差异。
