Genome-Wide Association Study Identifies a Functional SIDT2 Variant Associated With HDL-C (High-Density Lipoprotein Cholesterol) Levels and Premature Coronary Artery Disease
| العنوان: | Genome-Wide Association Study Identifies a Functional SIDT2 Variant Associated With HDL-C (High-Density Lipoprotein Cholesterol) Levels and Premature Coronary Artery Disease |
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| المؤلفون: | Francisco J. Flores-Murrieta, Roberto Nieto-Guerra, Hugo Villamil-Ramírez, Francisco Campos-Pérez, Luis Vaca, Rosalinda Posadas-Sánchez, Blanca E. López-Contreras, Samuel Canizales-Quinteros, Marisol Olivares-Arevalo, Gilberto Vargas-Alarcón, Israel González-González, Brian G. Drew, Mayra Domínguez-Pérez, Peter J. Meikle, Aldons J. Lusis, Sandra Romero-Hidalgo, Victor Acuña-Alonzo, Teresa Villarreal-Molina, Alicia Sampieri, Miriam del Carmen Carrasco-Portugal, Adriana Huertas-Vazquez, Leonor Jacobo-Albavera, Rodrigo Barquera-Lozano, Gastón Macín-Pérez, Anna C. Calkin, Blanca E. Del-Rio-Navarro, Carlos Posadas-Romero, Paola León-Mimila, Carlos A. Aguilar-Salinas, Francisco J. Gómez-Pérez, Luis Macías-Kauffer, Diana M. Shih, Juan Gerardo Reyes-García, Sofia Moran-Ramos, Víctor Valdés, Priscilla Lopez-Montoya |
| المصدر: | Arteriosclerosis, Thrombosis, and Vascular Biology : an Official Journal of the American Heart Association |
| بيانات النشر: | Ovid Technologies (Wolters Kluwer Health), 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, medicine.medical_specialty, education.field_of_study, Apolipoprotein B, Cholesterol, Population, Genome-wide association study, Biology, Cholesterol analog, Sterol transport, 03 medical and health sciences, chemistry.chemical_compound, 030104 developmental biology, 0302 clinical medicine, Endocrinology, High-density lipoprotein, chemistry, ABCA1, Internal medicine, medicine, biology.protein, lipids (amino acids, peptides, and proteins), Cardiology and Cardiovascular Medicine, education, 030217 neurology & neurosurgery |
| الوصف: | Objective: Low HDL-C (high-density lipoprotein cholesterol) is the most frequent dyslipidemia in Mexicans, but few studies have examined the underlying genetic basis. Our purpose was to identify genetic variants associated with HDL-C levels and cardiovascular risk in the Mexican population. Approach and Results: A genome-wide association studies for HDL-C levels in 2335 Mexicans, identified four loci associated with genome-wide significance: CETP , ABCA1 , LIPC , and SIDT2 . The SIDT2 missense Val636Ile variant was associated with HDL-C levels and was replicated in 3 independent cohorts ( P =5.9×10 −18 in the conjoint analysis). The SIDT2 /Val636Ile variant is more frequent in Native American and derived populations than in other ethnic groups. This variant was also associated with increased ApoA1 and glycerophospholipid serum levels, decreased LDL-C (low-density lipoprotein cholesterol) and ApoB levels, and a lower risk of premature CAD. Because SIDT2 was previously identified as a protein involved in sterol transport, we tested whether the SIDT2/Ile636 protein affected this function using an in vitro site-directed mutagenesis approach. The SIDT2/Ile636 protein showed increased uptake of the cholesterol analog dehydroergosterol, suggesting this variant affects function. Finally, liver transcriptome data from humans and the Hybrid Mouse Diversity Panel are consistent with the involvement of SIDT2 in lipid and lipoprotein metabolism. Conclusions: This is the first genome-wide association study for HDL-C levels seeking associations with coronary artery disease in the Mexican population. Our findings provide new insight into the genetic architecture of HDL-C and highlight SIDT2 as a new player in cholesterol and lipoprotein metabolism in humans. |
| وصف الملف: | application/pdf |
| تدمد: | 1524-4636 1079-5642 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0465fbaa0361c5af5b93c0643a2fb752Test https://doi.org/10.1161/atvbaha.120.315391Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....0465fbaa0361c5af5b93c0643a2fb752 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15244636 10795642 |
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