同型半胱氨酸代谢基因多态性与假性剥脱综合征及青光眼之间无关联。

Lack of association of polymorphisms in homocysteine metabolism genes with pseudoexfoliation syndrome and glaucoma.

作者信息

Fan Bao Jian, Chen Teresa, Grosskreutz Cynthia, Pasquale Louis, Rhee Douglas, DelBono Elizabeth, Haines Jonathan L, Wiggs Janey L

出版信息

Mol Vis. 2008;14:2484-91. Epub 2008 Dec 26.

DOI:

PMID:19112534

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2610294/

Abstract

PURPOSE

To evaluate genes involved in homocysteine metabolism as secondary risk factors for pseudoexfoliation syndrome (PXFS) and the associated glaucoma (PXFG).

METHODS

One hundred eighty-six unrelated patients with PXFS, including 140 patients with PXFG and 127 unrelated control subjects were recruited from the Massachusetts Eye and Ear Infirmary. All the patients and controls were Caucasian of European ancestry. Seventeen tag SNPs from 5 genes (methylenetetrahydrofolate reductase [MTHFR], methionine synthase [MTR], methionine synthase reductase [MTRR], methylenetetrahydrofolate dehydrogenase [MTHFD1], and cystathionine beta-synthase [CBS]) were genotyped. Single-SNP association was analyzed using Fisher's exact test (unconditional) or logistic regression after conditioning on the effects of age and three LOXL1 SNPs (rs1048661, rs3825942, and rs2165241). Interaction analysis was performed between the homocysteine and LOXL1 SNPs using logistic regression. Haplotype analysis and the set-based test were used to test for association of individual genes. Multiple comparisons were corrected using the Bonferroni method.

RESULTS

One SNP (rs8006686) in MTHFD1 showed a nominally significant association with PXFG (p=0.015, OR=2.23). None of the seventeen SNPs tested were significantly associated with PXFS or PXFG after correcting for multiple comparisons (Bonferroni corrected p>0.25). After controlling for the effects of age and three associated LOXL1 SNPs, none of the seventeen tested SNPs were associated with PXFS (p>0.12). No significant interaction effects on PXFS were identified between the homocysteine and LOXL1 SNPs (p>0.06). Haplotype analysis and the set-based test did not find significant association of individual genes with PXFS (p>0.23 and 0.20, respectively).

CONCLUSIONS

Five genes that are critical components of the homocysteine metabolism pathway were evaluated as secondary factors for PXFS and PXFG. Our results suggest that these genes are not significant risk factors for the development of these conditions.

摘要

目的

评估参与同型半胱氨酸代谢的基因作为假性剥脱综合征（PXFS）及相关青光眼（PXFG）的次要危险因素。

方法

从马萨诸塞州眼耳医院招募了186例无亲缘关系的PXFS患者，其中包括140例PXFG患者以及127例无亲缘关系的对照受试者。所有患者和对照均为欧洲血统的白种人。对来自5个基因（亚甲基四氢叶酸还原酶 [MTHFR]、甲硫氨酸合成酶 [MTR]、甲硫氨酸合成酶还原酶 [MTRR]、亚甲基四氢叶酸脱氢酶 [MTHFD1] 和胱硫醚β-合酶 [CBS]）的17个标签单核苷酸多态性（SNP）进行基因分型。使用Fisher精确检验（无条件）或在对年龄和三个LOXL1 SNP（rs1048661、rs3825942和rs2165241）的影响进行校正后进行逻辑回归分析单SNP关联。使用逻辑回归分析同型半胱氨酸和LOXL1 SNP之间的相互作用。使用单倍型分析和基于集合的检验来检验单个基因的关联性。使用Bonferroni方法校正多重比较。

结果

MTHFD1中的一个SNP（rs8006686）与PXFG显示出名义上的显著关联（p = 0.015，比值比 [OR]=2.23）。在进行多重比较校正后（Bonferroni校正p>0.25），所检测的17个SNP均与PXFS或PXFG无显著关联。在控制年龄和三个相关LOXL1 SNP的影响后，所检测的17个SNP均与PXFS无关联（p>0.12）。未发现同型半胱氨酸和LOXL1 SNP之间对PXFS有显著的相互作用效应（p>0.06）。单倍型分析和基于集合的检验未发现单个基因与PXFS有显著关联（分别为p>0.23和0.20）。