R230C but not − 565C/T variant of the ABCA1 gene is associated with type 2 diabetes in Mexicans through an effect on lowering HDL-cholesterol levels

Ochoa-Guzmán, Ana; Moreno-Macías, Hortensia; Guillén-Quintero, D.; Chávez-Talavera, Oscar; Ordonez-Sanchez, Ma. Luisa; Segura-Kato, Yayoi; Ortíz, Víctor; Díaz-Díaz, Eulises; Muñóz-Hernández, Liliana; Garcia, A. Sanchez; Pérez-Méndez, Óscar; Zentella‐Dehesa, Alejandro; Aguilar-Salinas, Carlos A.; Tusié-Luna, Marı́a Teresa

doi:10.1007/s40618-020-01187-8

Cited by 9 publications

(5 citation statements)

References 51 publications

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“…Recent data demonstrated that ABCA1 gene variants contribute to the development of type 2 diabetes by reducing serum HDL-C levels [79,80] and by increasing intracellular non-esterified cholesterol levels, leading to cell lipotoxicity and thus impaired pancreatic beta cell function [81][82][83][84][85]. Moreover ABCA1 gene downregulation reduces insulin-dependent Akt phosphorylation and GLUT4 translocation, affecting insulin sensitivity [46,48].…”

Section: Cell Lipotoxicity Apoptosismentioning

confidence: 99%

HDL and type 2 diabetes: the chicken or the egg?

et al. 2021

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HDL is a complex macromolecular cluster of various components, such as apolipoproteins, enzymes and lipids. Quality evidence from clinical and epidemiological studies led to the principle that HDL-cholesterol (HDL-C) levels are inversely correlated with the risk of CHD. Nevertheless, the failure of many cholesteryl ester transfer protein inhibitors to protect against CVD casts doubts on this principle and highlights the fact that HDL functionality, as dictated by its proteome and lipidome, also plays an important role in protecting against metabolic disorders. Recent data indicate that HDL-C levels and HDL particle functionality are correlated with the pathogenesis and prognosis of type 2 diabetes mellitus, a major risk factor for CVD. Hyperglycaemia leads to reduced HDL-C levels and deteriorated HDL functionality, via various alterations in HDL particles' proteome and lipidome. In turn, reduced HDL-C levels and impaired HDL functionality impact the performance of key organs related to glucose homeostasis, such as pancreas and skeletal muscles. Interestingly, different structural alterations in HDL correlate with distinct metabolic abnormalities, as indicated by recent data evaluating the role of apolipoprotein A1 and lecithin-cholesterol acyltransferase deficiency in glucose homeostasis. While it is becoming evident that not all HDL disturbances are causatively associated with the development and progression of type 2 diabetes, a bidirectional correlation between these two conditions exists, leading to a perpetual self-feeding cycle.

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Section: Cell Lipotoxicity Apoptosismentioning

confidence: 99%

HDL and type 2 diabetes: the chicken or the egg?

et al. 2021

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“…Consistently with this idea, patients with Tangier disease are characterized by an impaired HDL-mediated lipid efflux [126,127] and concomitant glucose intolerance and decreased insulin secretion [128]. In the same vein, the ABC-A1 polymorphism rs9282541 that results in a substitution of arginine 230 for cysteine is associated with the increased incidence of type 2 diabetes mediated by HDL cholesterol plasma levels [129]. Finally, a recent meta-analysis demonstrated that CETP inhibitors decrease the risk of new-onset of diabetes by 16%, concomitantly with significant increases in HDL-C [130].…”

Section: Hdl Contribution To Insulin Secretionmentioning

confidence: 77%

HDL as Bidirectional Lipid Vectors: Time for New Paradigms

Luna-Luna

Niesor²,

Pérez-Méndez

2022

Biomedicines

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The anti-atherogenic properties of high-density lipoproteins (HDL) have been explained mainly by reverse cholesterol transport (RCT) from peripheral tissues to the liver. The RCT seems to agree with most of the negative epidemiological correlations between HDL cholesterol levels and coronary artery disease. However, therapies designed to increase HDL cholesterol failed to reduce cardiovascular risk, despite their capacity to improve cholesterol efflux, the first stage of RCT. Therefore, the cardioprotective role of HDL may not be explained by RCT, and it is time for new paradigms about the physiological function of these lipoproteins. It should be considered that the main HDL apolipoprotein, apo AI, has been highly conserved throughout evolution. Consequently, these lipoproteins play an essential physiological role beyond their capacity to protect against atherosclerosis. We propose HDL as bidirectional lipid vectors carrying lipids from and to tissues according to their local context. Lipid influx mediated by HDL appears to be particularly important for tissue repair right on site where the damage occurs, including arteries during the first stages of atherosclerosis. In contrast, the HDL-lipid efflux is relevant for secretory cells where the fusion of intracellular vesicles drastically enlarges the cytoplasmic membrane with the potential consequence of impairment of cell function. In such circumstances, HDL could deliver some functional lipids and pick up not only cholesterol but an integral part of the membrane in excess, restoring the viability of the secretory cells. This hypothesis is congruent with the beneficial effects of HDL against atherosclerosis as well as with their capacity to induce insulin secretion and merits experimental exploration.

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“…However, the literature has also shown varying results; some studies have associated the rs9282541 variant equally in males and females [ 25 ]. Other studies on CVD found a more significant association among males [ 27 ]. Possible explanations for these inconsistencies are the sample size, the spurious associations due to population stratification, analyses lacking an adjustment for confounders, or differences in the study design.…”

Section: Discussionmentioning

confidence: 92%

“…The missense polymorphism rs9282541 (alleles G/A) within ABCA1 is relevant for the Mexican population because the rs9282541-A allele is almost exclusive to Native American people (~4%), while on other continents, it has not been found. The rs9282541-A allele has been associated with decreased HDL-c levels and cholesterol efflux in vitro (~27%), obesity, CVD, and T2D in the Mexican population [ 24 , 25 , 26 , 27 ]. Nevertheless, the pathophysiological mechanisms of these loci associated with the variations in HDL-c concentrations remain unknown.…”

Section: Introductionmentioning

confidence: 99%

Interaction between SIDT2 and ABCA1 Variants with Nutrients on HDL-c Levels in Mexican Adults

et al. 2023

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Previous studies have reported that the SIDT2 and ABCA1 genes are involved in lipid metabolism. We aimed to analyze the association—the gene x gene interaction between rs17120425 and rs1784042 on SIDT2 and rs9282541 on ABCA1 and their diet interaction on the HDL-c serum levels—in a cohort of 1982 Mexican adults from the Health Workers Cohort Study. Demographic and clinical data were collected through a structured questionnaire and standardized procedures. Genotyping was performed using a predesigned TaqMan assay. The associations and interactions of interest were estimated using linear and logistic regression. Carriers of the rs17120425-A and rs1784042-A alleles had slightly higher blood HDL-c levels compared to the non-carriers. In contrast, rs9282541-A was associated with low blood HDL-c levels (OR = 1.34, p = 0.013). The rs1784042 x rs9282541 interaction was associated with high blood HDL-c levels (p = 3.4 × 10−4). Premenopausal women who carried at least one rs17120425-A allele and consumed high dietary fat, protein, monounsaturated, or polyunsaturated fatty acids levels had higher HDL-c levels than the non-carriers. These results support the association between the genetic variants on SIDT2 and ABCA1 with HDL-c levels and suggest gene–gene and gene–diet interactions over HDL-c concentrations in Mexican adults. Our findings could be a platform for developing clinical and dietary strategies for improving the health of the Mexican population.

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R230C but not − 565C/T variant of the ABCA1 gene is associated with type 2 diabetes in Mexicans through an effect on lowering HDL-cholesterol levels

Cited by 9 publications

References 51 publications

HDL and type 2 diabetes: the chicken or the egg?

HDL and type 2 diabetes: the chicken or the egg?

HDL as Bidirectional Lipid Vectors: Time for New Paradigms

Interaction between SIDT2 and ABCA1 Variants with Nutrients on HDL-c Levels in Mexican Adults

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