The -514C>T polymorphism in the LIPC gene modifies type 2 diabetes risk through modulation of HDL-cholesterol levels in Mexicans.

Autor: Guerra-García MT; Unit of Molecular Biology and Genomic Medicine, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga #15, Belisario Domínguez, Sección XVI, Tlalpan, 14080, Mexico City, Mexico., Moreno-Macías H; Unit of Molecular Biology and Genomic Medicine, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga #15, Belisario Domínguez, Sección XVI, Tlalpan, 14080, Mexico City, Mexico.; Economy Department, Universidad Autónoma Metropolitana, Mexico City, Mexico., Ochoa-Guzmán A; Unit of Molecular Biology and Genomic Medicine, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga #15, Belisario Domínguez, Sección XVI, Tlalpan, 14080, Mexico City, Mexico., Ordoñez-Sánchez ML; Unit of Molecular Biology and Genomic Medicine, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga #15, Belisario Domínguez, Sección XVI, Tlalpan, 14080, Mexico City, Mexico., Rodríguez-Guillen R; Unit of Molecular Biology and Genomic Medicine, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga #15, Belisario Domínguez, Sección XVI, Tlalpan, 14080, Mexico City, Mexico., Vázquez-Cárdenas P; Obesity Clinic, Hospital General Dr. Manuel Gea González, Mexico City, Mexico., Ortíz-Ortega VM; Department of Physiology of Nutrition, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico., Peimbert-Torres M; Nature Sciences Department, Universidad Autónoma Metropolitana, Mexico City, Mexico., Aguilar-Salinas CA; Division of Nutrition, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico., Tusié-Luna MT; Unit of Molecular Biology and Genomic Medicine, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga #15, Belisario Domínguez, Sección XVI, Tlalpan, 14080, Mexico City, Mexico. mttusie@gmail.com.; Instituto de Investigaciones Biomédicas, Univesidad Nacional Autónoma de México, Mexico City, Mexico. mttusie@gmail.com.
Jazyk: angličtina
Zdroj: Journal of endocrinological investigation [J Endocrinol Invest] 2021 Mar; Vol. 44 (3), pp. 557-565. Date of Electronic Publication: 2020 Jul 02.
DOI: 10.1007/s40618-020-01346-x
Abstrakt: Purpose: Both type 2 diabetes (T2D) and low levels of high-density lipoprotein cholesterol (HDL-C) are very prevalent conditions among Mexicans. Genetic variants in the LIPC gene have been associated with both conditions. This study aimed to evaluate the association of the -514C < T (rs1800588) LIPC gene polymorphism with different metabolic traits, particularly the effects of this polymorphism on HDL-C plasma levels and T2D risk.
Methods: Mediation analysis was used to assess the direct and indirect effects of the -514C>T LIPC gene variant on HDL-C levels, T2D risk, and body mass index (BMI), in 2105 Mexican mestizo participants. We also assessed the functional effect of the -514C>T LIPC variant on the promoter activity of a reporter gene in the HepG2 cell line.
Results: Direct effects show that the -514C>T LIPC polymorphism is significantly associated with increased HDL-C plasma levels (β = 0.03; p < 0.001). The -514C>T variant resulted in an indirect protective effect on T2D risk through increasing HDL-C levels (β = - 0.03; p < 0.001). Marginal direct association between -514C>T and T2D was found (β = 0.08; p = 0.06). Variables directly influencing T2D status were European ethnicity (β = - 7.20; p < 0.001), age (β = 0.04; p < 0.001), gender (β = - 0.15; p = 0.017) and HDL-C (β = - 1.07; p < 0.001). In addition, we found that the -514C>T variant decreases the activity of LIPC promoter by 90% (p < 0.001).
Conclusions: The -514C>T polymorphism was not directly associated with T2D risk. HDL-C acts as a mediator between -514C>T LIPC gene variant and T2D risk in the Mexican population.
Databáze: MEDLINE
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