Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin 300384, China.
Nutrients. 2023 Sep 29;15(19):4208. doi: 10.3390/nu15194208.
Polyunsaturated fatty acids (PUFAs) affect several physiological processes, including visual acuity, but their relationship with diabetic retinopathy (DR) remains elusive. The aim of this study was to determine whether PUFAs have a causal effect on DR. PUFAs- (total and omega-3 [FAw3] and omega-6 [FAw6] fatty acids and their ratio) and DR-associated single nucleotide polymorphisms derived from genome-wide association studies; sample sizes were 114,999 for fatty acids and 216,666 for any DR (ADR), background DR (BDR), severe non-proliferative DR (SNPDR), and proliferative DR (PDR). We hypothesized that the intra-body levels of PUFAs have an impact on DR and conducted a two-sample Mendelian randomization (MR) study to assess the causality. Pleiotropy, heterogeneity, and sensitivity analyses were performed to verify result reliability. High levels of PUFAs were found to be associated with reduced risk of both ADR and PDR. Moreover, FAw3 was associated with a decreased risk of PDR, whereas FAw6 demonstrated an association with lowered risks of both BDR and PDR. Our findings provide genetic evidence, for the first time, for a causal relationship between PUFAs and reduced DR risk. Consequently, our comprehensive MR analysis strongly urges further investigation into the precise functions and long-term effects of PUFAs, FAw3, and FAw6 on DR.
多不饱和脂肪酸（PUFAs）影响多种生理过程，包括视力，但它们与糖尿病视网膜病变（DR）的关系仍不清楚。本研究旨在确定 PUFAs 是否对 DR 有因果影响。从全基因组关联研究中得出的 PUFAs（总 PUFAs 和 ω-3 [FAw3] 和 ω-6 [FAw6] 脂肪酸及其比值）和与 DR 相关的单核苷酸多态性；脂肪酸的样本量为 114999，任何 DR（ADR）、背景 DR（BDR）、严重非增殖性 DR（SNPDR）和增殖性 DR（PDR）的样本量为 216666。我们假设体内 PUFAs 水平对 DR 有影响，并进行了两样本孟德尔随机化（MR）研究来评估因果关系。进行了多效性、异质性和敏感性分析以验证结果的可靠性。高水平的 PUFAs 与 ADR 和 PDR 的风险降低有关。此外，FAw3 与 PDR 风险降低有关，而 FAw6 与 BDR 和 PDR 的风险降低有关。我们的研究结果首次提供了 PUFAs 与 DR 风险降低之间存在因果关系的遗传证据。因此，我们的综合 MR 分析强烈呼吁进一步研究 PUFAs、FAw3 和 FAw6 对 DR 的精确功能和长期影响。
