Division of Endocrinology and Metabolism, Department of Internal Medicine, Toshiba Rinkan Hospital, 7-9-1 Kami-tsuruma, Minami-ku, Sagamihara, Kanagawa, 252-0385, Japan.
Department of Endocrinology, Diabetes and Metabolism, Kitasato University School of Medicine, Sagamihara, Japan.
Acta Diabetol. 2022 Mar;59(3):319-327. doi: 10.1007/s00592-021-01808-5. Epub 2021 Oct 14.
To investigate the effects of single-nucleotide polymorphisms (SNPs) around the protein arginine N-methyltransferase 1 (PRMT1) gene on the incidence and severity of diabetic retinopathy (DR).
A total of 310 Japanese patients with type 2 diabetes mellitus (T2DM) were investigated. Genotyping of ten tagged SNPs were performed by quantitative real-time polymerase chain reaction (qRT-PCR). The association between each SNP genotype and diabetic microangiopathy was assessed using univariate analysis in a dominant model of the minor alleles followed by multivariate logistic regression analysis with the propensity score matching (PSM) method. The effect of disease-related SNP on PRMT1 and hypoxia-inducible factor-1α (HIF-1α) mRNA levels in vivo was evaluated by qRT-PCR.
In the univariate analysis, the minor A allele at rs374569 and the minor C allele at rs3745468 were associated with DR severity (P = 0.047 and P = 0.003, respectively), but not diabetic nephropathy and peripheral polyneuropathy severity. Multivariate analysis showed that the rs3745468 variant caused an increased incidence of proliferative DR (PDR) (odds ratio 9.37, 95% confidence interval 1.12-78.0, P = 0.039). In the PSM cohort, the patients carrying the rs3745468 variant had lower PRMT1 mRNA levels compared to those without the variant (P = 0.037), and there was an inverse correlation between PRMT1 and HIF-1α mRNA levels (r = -0.233, P = 0.035).
The rs3745468 variant in the PRMT1 gene was associated with an increased incidence of PDR in Japanese patients with T2DM and might be involved in the HIF-1-dependent hypoxic pathway through altered PRMT1 levels.
研究蛋白精氨酸 N-甲基转移酶 1（PRMT1）基因周围单核苷酸多态性（SNP）对糖尿病视网膜病变（DR）发生和严重程度的影响。
共调查了 310 名日本 2 型糖尿病（T2DM）患者。通过实时定量聚合酶链反应（qRT-PCR）对十个标记 SNP 的基因型进行检测。采用优势等位基因的显性模型进行单变量分析，然后采用倾向评分匹配（PSM）法进行多变量逻辑回归分析，评估每个 SNP 基因型与糖尿病微血管病变的相关性。通过 qRT-PCR 评估疾病相关 SNP 对体内 PRMT1 和缺氧诱导因子-1α（HIF-1α）mRNA 水平的影响。
在单变量分析中，rs374569 的次要 A 等位基因和 rs3745468 的次要 C 等位基因与 DR 严重程度相关（P=0.047 和 P=0.003），但与糖尿病肾病和周围多发性神经病严重程度无关。多变量分析显示，rs3745468 变异使增殖性 DR（PDR）的发生率增加（优势比 9.37，95%置信区间 1.12-78.0，P=0.039）。在 PSM 队列中，与没有变异的患者相比，携带 rs3745468 变异的患者的 PRMT1 mRNA 水平较低（P=0.037），并且 PRMT1 和 HIF-1α mRNA 水平之间存在负相关（r=-0.233，P=0.035）。
PRMT1 基因中的 rs3745468 变异与日本 T2DM 患者 PDR 的发生率增加有关，并且可能通过改变 PRMT1 水平参与 HIF-1 依赖性缺氧途径。
