促红细胞生成素基因多态性与糖尿病视网膜病变的相关性：病例对照研究和系统评价Meta 分析。
Association of polymorphisms in the erythropoietin gene with diabetic retinopathy: a case-control study and systematic review with meta-analysis.
机构信息
Lutheran University Center of Palmas, Universidade Luterana do Brasil (ULBRA), Palmas, TO, Brazil.
Laboratory of Human Molecular Genetics, Programa de Pós-Graduação em Biologia Celular e Molecular Aplicada à Saúde (PPGBioSaúde), Universidade Luterana do Brasil (ULBRA), Av. Farroupilha, 8001, Prédio 22, 5° andar, Canoas, RS, 92425-900, Brazil.
出版信息
BMC Ophthalmol. 2022 Jun 4;22(1):250. doi: 10.1186/s12886-022-02467-y.
BACKGROUND
Diabetic retinopathy (DR) is characterized by ischemia, hypoxia, and angiogenesis. Erythropoietin (EPO), an angiogenic hormone, is upregulated in DR, and the association of EPO genetic variants with DR is still uncertain, as conflicting results have been reported. Therefore, we performed a case-control study followed by a meta-analysis to investigate whether the rs1617640, rs507392, and rs551238 polymorphisms in EPO gene are associated with DR.
METHODS
The case-control study included 1042 Southern Brazilians with type 2 diabetes (488 without DR and 554 with DR). Eligible studies for the meta-analysis were searched from electronic databases up to June 1, 2021. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for five genetic inheritance models.
RESULTS
The minor alleles of the EPO polymorphisms had nearly the same frequency in all groups of patients (35%), and no association was detected with DR in the case-control study. The meta-analysis included 14 independent sets of cases and controls with 9117 subjects for the rs1617640 polymorphism and nine independent sets with more than 5000 subjects for the rs507392 and rs551238 polymorphisms. The G allele of the rs1617640 polymorphism was suggestively associated with DR under the dominant (OR = 0.82, 95% CI: 0.68-0.98), heterozygous additive (OR = 0.82, 95% CI: 0.69-0.97), and overdominant (OR = 0.88, 95% CI: 0.79-0.97) models. In the subgroup analyses, the G allele was also suggestively associated with proliferative DR (PDR), non-proliferative DR (NPDR), and DR (PDR + NPDR) among patients with type 1 diabetes (T1DM) or non-Asian ancestry. After considering the Bonferroni correction for multiple comparisons, the G allele remained associated with NPDR and DR in T1DM. Regarding the rs507392 and rs551238 polymorphisms, no association was found between these variants and DR.
CONCLUSION
Our findings provide additional support to EPO as a susceptibility gene for DR, with the rs1617640 polymorphism deserving further investigation.
背景
糖尿病视网膜病变（DR）的特征是缺血、缺氧和血管生成。促红细胞生成素（EPO）是一种血管生成激素，在 DR 中上调，EPO 基因的遗传变异与 DR 的关联尚不确定，因为已有相互矛盾的结果报道。因此，我们进行了病例对照研究，并进行了荟萃分析，以调查 EPO 基因中的 rs1617640、rs507392 和 rs551238 多态性是否与 DR 相关。
方法
该病例对照研究纳入了 1042 名来自巴西南部的 2 型糖尿病患者（488 名无 DR，554 名有 DR）。对截至 2021 年 6 月 1 日的电子数据库中的合格研究进行了荟萃分析。使用五种遗传遗传模型估计了 EPO 多态性的合并优势比（OR）和 95%置信区间（CI）。
结果
EPO 多态性的次要等位基因在所有患者组中的频率几乎相同（35%），并且在病例对照研究中未发现与 DR 相关。荟萃分析纳入了 rs1617640 多态性的 14 个独立病例对照集，包含 9117 名受试者，rs507392 和 rs551238 多态性的九个独立病例对照集包含 5000 多名受试者。rs1617640 多态性的 G 等位基因在显性（OR=0.82，95%CI：0.68-0.98）、杂合子加性（OR=0.82，95%CI：0.69-0.97）和超显性（OR=0.88，95%CI：0.79-0.97）模型中与 DR 呈提示性关联。在亚组分析中，G 等位基因也与 1 型糖尿病（T1DM）或非亚洲血统患者的增殖性 DR（PDR）、非增殖性 DR（NPDR）和 DR（PDR+NPDR）呈提示性关联。考虑到多次比较的 Bonferroni 校正后，G 等位基因在 T1DM 中仍与 NPDR 和 DR 相关。关于 rs507392 和 rs551238 多态性，未发现这些变体与 DR 之间存在关联。
结论
我们的研究结果为 EPO 作为 DR 的易感基因提供了额外的支持，rs1617640 多态性值得进一步研究。
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