Coronary artery disease (CAD) is the leading cause of death worldwide despite advanced treatment and diagnosis strategies. Angiopoietin-like protein 8 (ANGPTL8) mainly functions in the lipid mechanism, which is a dysregulated mechanism during CAD pathogenesis. In this study, we aimed to determine the associations between an polymorphism rs2278426 and the severity, presence, and risk factors of CAD. A total of 1367 unrelated Turkish individuals who underwent coronary angiography were recruited for the study and grouped as CAD (n = 736, ≥50 stenosis) and non-CAD (n = 549, ≤30 stenosis). Also, subjects were further divided into groups regarding type 2 diabetes mellitus (T2DM) status. Subjects were genotyped for rs2278426 (C/T) by quantitative real-time PCR. Secondary structure analyses of protein interactions were revealed using I-TASSER and PyMOL. Among CAD patients, T allele carriage frequency was lower in the T2DM group (). Moreover, in male non-CAD group, T allele carriage was more prevalent among T2DM patients than non-T2DM (). In logistic regression analysis adjusted for obesity, T allele carrier males had an increased risk for T2DM in non-CAD group (OR = 2.244, 95 % CI: 1.057–4.761, 035). Also, in T2DM group, stenosis () and SYNTAX score ( = 0.040) were lower in T allele carrier males than in non-carriers. Analyzes of secondary structure showed that ANGPTL8 could not directly form complexes with ANGPTL3 or ANGPTL4. In conclusion, T allele carriage of rs2278426 has a protective effect on CAD in T2DM patients. Further research should be conducted to explore the association between polymorphism rs2778426) and CAD.

中文翻译：

---

ANGPTL8 rs2278426 的小等位基因对 T2DM 患者的 CAD 具有保护作用

尽管治疗和诊断策略先进，但冠状动脉疾病 (CAD) 仍是全世界死亡的主要原因。血管生成素样蛋白 8 (ANGPTL8) 主要在脂质机制中发挥作用，脂质机制是 CAD 发病过程中的失调机制。在本研究中，我们旨在确定 rs2278426 多态性与 CAD 的严重程度、存在和危险因素之间的关联。该研究共招募了 1367 名接受冠状动脉造影的无关土耳其人，并分为 CAD（n = 736，≥50 狭窄）和非 CAD（n = 549，≤ 30 狭窄）。此外，受试者还根据 2 型糖尿病 (T2DM) 状态进一步分组。通过实时定量 PCR 对受试者进行 rs2278426 (C/T) 基因分型。使用 I-TASSER 和 PyMOL 揭示了蛋白质相互作用的二级结构分析。在 CAD 患者中，T 等位基因携带频率在 T2DM 组中较低 ()。此外，在男性非 CAD 组中，T 等位基因携带在 T2DM 患者中比非 T2DM 患者中更为普遍。在针对肥胖进行调整的逻辑回归分析中，T 等位基因携带者男性在非 CAD 组中患 T2DM 的风险增加（OR = 2.244，95 % CI：1.057–4.761, 035）。此外，在 T2DM 组中，T 等位基因携带者男性的狭窄 () 和 SYNTAX 评分 (= 0.040) 低于非携带者。二级结构分析表明ANGPTL8不能直接与ANGPTL3或ANGPTL4形成复合物。总之，rs2278426 的 T 等位基因携带对 T2DM 患者的 CAD 具有保护作用。应进一步研究探索多态性（rs2778426）与 CAD 之间的关联。