The minor allele of ANGPTL8 rs2278426 has a protective effect against CAD in T2DM patients

• Published in: Gene Vol. 914; p. 148418
• Main Authors: Bilgin, Aslihan Gizem, Ekici, Berkay, Ozuynuk-Ertugrul, Aybike Sena, Erkan, Aycan Fahri, Coban, Neslihan
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.07.2024
• Subjects: Aged; Alleles; angiography; Angiopoietin-Like Protein 8; Angiopoietin-like Proteins - genetics; ANGPTL8; CAD; Coronary Angiography; coronary artery disease; Coronary Artery Disease - genetics; death; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - genetics; Female; Gene Frequency; Genetic Predisposition to Disease; genotyping; Humans; lipids; Male; males; Middle Aged; noninsulin-dependent diabetes mellitus; obesity; pathogenesis; Peptide Hormones - genetics; Polymorphism; Polymorphism, Single Nucleotide; protective effect; quantitative polymerase chain reaction; regression analysis; risk; Risk Factors; Rs2278426; T2DM; Turkey; Turkey; T2DM; HDL; TG; LDL; ANGPTL8; CAD; LPL; Rs2278426; PCR; Polymorphism; BMI
• DOI: 10.1016/j.gene.2024.148418
• ISSN: 0378-1119; 1879-0038

[Display omitted] •Minor allele frequency of rs2278426 was measured as 10.18% in Turkish individuals.•T allele carriage has a protective effect against T2DM in CAD group.•T allele carrier T2DM patients had lower stenosis percentages in the CAD group.•ANGPTL8 could not directly bind to ANGPTL3/4 according to in silico analysis. 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 ANGPTL8 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 (p = 0.046). Moreover, in male non-CAD group, T allele carriage was more prevalent among T2DM patients than non-T2DM (p = 0.033). 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, p = 0.035). Also, in T2DM group, stenosis (p = 0.002) and SYNTAX score (p = 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 ANGPTL8 rs2278426 has a protective effect on CAD in T2DM patients. Further research should be conducted to explore the association between ANGPTL8 polymorphism (rs2778426) and CAD.