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谷胱甘肽S-转移酶ω-2基因多态性Asn142Asp改变吸烟者及紫外线照射人群患年龄相关性白内障的风险。

Glutathione S-transferase omega-2 polymorphism Asn142Asp modifies the risk of age-related cataract in smokers and subjects exposed to ultraviolet irradiation.

作者信息

Stamenkovic Miroslav, Radic Tanja, Stefanovic Ivan, Coric Vesna, Sencanic Ivan, Pljesa-Ercegovac Marija, Matic Marija, Jaksic Vesna, Simic Tatjana, Savic-Radojevic Ana

机构信息

Medical Center Zvezdara, University Eye Clinic, Belgrade, Serbia; Faculty of Special Education and Rehabiltation, University of Belgrade, Belgrade, Serbia.

出版信息

Clin Exp Ophthalmol. 2014 Apr;42(3):277-83. doi: 10.1111/ceo.12180. Epub 2013 Sep 24.

DOI:10.1111/ceo.12180
PMID:23927022
Abstract

BACKGROUND

Glutathione S-transferase omega-1 and 2 have a unique range of enzymatic activities, including the regeneration of ascorbate by their dehydroascorbate reductase activities. Because these enzymes could have a protective role from oxidative damage in the lens, the question of whether the two coding glutathione S-transferase omega polymorphisms confer the risk of age-related cataract was addressed.

METHODS

rs4925 (Ala140Asp) of glutathione S-transferase omega-1 and rs156697 (Asn142Asp) of glutathione S-transferase omega-2 polymorphisms in 100 patients with age-related cataract and 130 controls were assessed.

RESULTS

Presence of one mutant GSTO1Asp or GSTO2Asp allele did not contribute independently towards the risk of cataract; however, homozygous carriers of GSTO1Asp/GSTO2Asp haplotype demonstrated 3.42-fold enhanced risk of cataract development (95% confidence interval = 0.84-13.93; P = 0.086). When GSTO genotype was analysed in association with smoking or professional exposure to ultraviolet irradiation, carriers of at least one mutant GSTO2Asp allele had increased risk of cataract development in comparison with individuals with wild-type GSTO2Asn/Asn with no history of smoking or ultraviolet exposure (odds ratio = 6.89, 95% confidence interval = 1.81-16.21, P = 0.005; odds ratio = 4.10, 95% confidence interval = 1.23-13.74, P = 0.022, respectively). Regarding the distribution of particular glutathione S-transferase omega genotype and cataract type, the highest frequency of mutant GSTO2*Asp allele was found in patients with nuclear cataract.

CONCLUSION

The results indicate that mutant GSTO2*Asp genotype is associated with increased risk of age-related cataract in smokers and ultraviolet-exposed subjects, suggesting a role of inefficient ascorbate regeneration in cataract development.

摘要

背景

谷胱甘肽S-转移酶ω-1和ω-2具有独特的酶活性范围,包括通过其脱氢抗坏血酸还原酶活性再生抗坏血酸。由于这些酶可能对晶状体氧化损伤具有保护作用,因此研究了两种编码谷胱甘肽S-转移酶ω多态性是否会增加年龄相关性白内障的风险。

方法

对100例年龄相关性白内障患者和130例对照者的谷胱甘肽S-转移酶ω-1的rs4925(Ala140Asp)和谷胱甘肽S-转移酶ω-2的rs156697(Asn142Asp)多态性进行评估。

结果

存在一个突变的GSTO1Asp或GSTO2Asp等位基因并不会独立增加患白内障的风险;然而,GSTO1Asp/GSTO2Asp单倍型的纯合携带者患白内障的风险增加了3.42倍(95%置信区间=0.84-13.93;P=0.086)。当分析GSTO基因型与吸烟或职业性紫外线照射的关系时,与无吸烟或紫外线暴露史的野生型GSTO2Asn/Asn个体相比,至少携带一个突变的GSTO2Asp等位基因的携带者患白内障的风险增加(优势比分别为6.89,95%置信区间=1.81-16.21,P=0.005;优势比为4.10,95%置信区间=1.23-13.74,P=0.022)。关于特定谷胱甘肽S-转移酶ω基因型与白内障类型的分布,在核性白内障患者中发现突变的GSTO2*Asp等位基因频率最高。

结论

结果表明,突变的GSTO2*Asp基因型与吸烟和紫外线暴露人群年龄相关性白内障风险增加有关,提示抗坏血酸再生效率低下在白内障发生发展中起作用。

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