Reduced Expression of ATP-Binding Cassette Transporter G1 Increases Cholesterol Accumulation in Macrophages of Patients With Type 2 Diabetes Mellitus

Background. Type 2 diabetes mellitus (T2DM) is a complex polygenic disorder characterized by impaired insulin resistance, insulin secretion, and dysregulation of lipid and protein metabolism with environmental and genetic factors. ATP-binding cassette transporter A1 (ABCA1) gene polymorphisms are reported as the one of the genetic risk factors for T2DM in various populations with conflicting results. This study was conducted based on PCR-HRM to determine the frequency of ABCA1 gene by rs2230806 (R219K), rs1800977 (C69T), and rs9282541 (R230C) polymorphisms Malaysian subjects.Methods. A total of 164 T2DM and 165 controls were recruited and their genotypes for ABCA1 gene polymorphisms were determined based on the real time high resolution melting analysis.Results. There was a significant difference between the subjects in terms of age, BMI, FPG, HbA1c, HDL, LDL, and TGP<0.05. There was a significant association between HOM of R219KP=0.005, among Malaysian subjects; moreover, allele frequency revealed the significant difference in A allele of R219KP=0.003. But, there was no significant difference in genotypic and allelic frequencies of C69T and R230C polymorphism.Conclusion. R219K polymorphism of ABCA1 gene can be considered as a genetic risk factor for T2DM subjects among Malaysians.

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The R230C variant of the ATP binding cassette protein A1 (ABCA1) gene is associated with a decreased response to glyburide therapy in patients with type 2 diabetes mellitus

Metabolism ◽

10.1016/j.metabol.2012.11.006 ◽

2013 ◽

Vol 62 (5) ◽

pp. 638-641 ◽

Cited By ~ 4

Author(s):

Carlos A. Aguilar-Salinas ◽

Linda Liliana Muñoz-Hernandez ◽

Monica Cobos-Bonilla ◽

Marcos Rafael Ramírez-Márquez ◽

Maria Luisa Ordoñez-Sanchez ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Atp Binding ◽

Abca1 Gene ◽

Atp Binding Cassette

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The ATP-Binding Cassette Transporter Subfamily A Member 1 (ABC-A1) and Type 2 Diabetes: An Association Beyond HDL Cholesterol

Current Diabetes Reviews ◽

10.2174/157339907782329979 ◽

2007 ◽

Vol 3 (4) ◽

pp. 264-267 ◽

Cited By ~ 17

Author(s):

Carlos Aguilar Salinas ◽

Ivette Cruz-Bautista ◽

Roopa Mehta ◽

Ma Villarreal-Molina ◽

Francisco Perez ◽

...

Keyword(s):

Type 2 Diabetes ◽

Hdl Cholesterol ◽

Atp Binding ◽

Atp Binding Cassette Transporter ◽

Atp Binding Cassette

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ATP-Binding Cassette Transporter A1 Polymorphisms and Haplotypes in Risk of Type 2 Diabetes

Gene Cell and Tissue ◽

10.17795/gct-43677 ◽

2016 ◽

Vol 4 (1) ◽

Cited By ~ 2

Author(s):

Ramin Saravani ◽

Hamid Reza Galavi ◽

Nasrin Ranjbar ◽

Ali Reza Alamdari

Keyword(s):

Type 2 Diabetes ◽

Atp Binding ◽

Atp Binding Cassette Transporter ◽

Atp Binding Cassette

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Association of the ATP-Binding Cassette Transporter A1 R230C Variant With Early-Onset Type 2 Diabetes in a Mexican Population

Diabetes ◽

10.2337/db07-0484 ◽

2007 ◽

Vol 57 (2) ◽

pp. 509-513 ◽

Cited By ~ 68

Author(s):

M. T. Villarreal-Molina ◽

M. T. Flores-Dorantes ◽

O. Arellano-Campos ◽

M. Villalobos-Comparan ◽

M. Rodriguez-Cruz ◽

...

Keyword(s):

Type 2 Diabetes ◽

Early Onset ◽

Mexican Population ◽

Atp Binding ◽

Onset Type ◽

Atp Binding Cassette Transporter ◽

Atp Binding Cassette

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Diabetes Impairs Cellular Cholesterol Efflux From ABCA1 to Small HDL Particles

Circulation Research ◽

10.1161/circresaha.120.317178 ◽

2020 ◽

Vol 127 (9) ◽

pp. 1198-1210 ◽

Cited By ~ 1

Author(s):

Yi He ◽

Graziella E. Ronsein ◽

Chongren Tang ◽

Gail P. Jarvik ◽

W. Sean Davidson ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Cholesterol Efflux ◽

Disease Risk ◽

Cardiovascular Disease Risk ◽

Cellular Cholesterol ◽

Atp Binding Cassette Transporter ◽

Cellular Cholesterol Efflux

Rationale: HDL (high-density lipoprotein) may be cardioprotective because it accepts cholesterol from macrophages via the cholesterol transport proteins ABCA1 (ATP-binding cassette transporter A1) and ABCG1 (ATP-binding cassette transporter G1). The ABCA1-specific cellular cholesterol efflux capacity (ABCA1 CEC) of HDL strongly and negatively associates with cardiovascular disease risk, but how diabetes mellitus impacts that step is unclear. Objective: To test the hypothesis that HDL’s cholesterol efflux capacity is impaired in subjects with type 2 diabetes mellitus. Methods and Results: We performed a case-control study with 19 subjects with type 2 diabetes mellitus and 20 control subjects. Three sizes of HDL particles, small HDL, medium HDL, and large HDL, were isolated by high-resolution size exclusion chromatography from study subjects. Then we assessed the ABCA1 CEC of equimolar concentrations of particles. Small HDL accounted for almost all of ABCA1 CEC activity of HDL. ABCA1 CEC―but not ABCG1 CEC―of small HDL was lower in the subjects with type 2 diabetes mellitus than the control subjects. Isotope dilution tandem mass spectrometry demonstrated that the concentration of SERPINA1 (serpin family A member 1) in small HDL was also lower in subjects with diabetes mellitus. Enriching small HDL with SERPINA1 enhanced ABCA1 CEC. Structural analysis of SERPINA1 identified 3 amphipathic α-helices clustered in the N-terminal domain of the protein; biochemical analyses demonstrated that SERPINA1 binds phospholipid vesicles. Conclusions: The ABCA1 CEC of small HDL is selectively impaired in type 2 diabetes mellitus, likely because of lower levels of SERPINA1. SERPINA1 contains a cluster of amphipathic α-helices that enable apolipoproteins to bind phospholipid and promote ABCA1 activity. Thus, impaired ABCA1 activity of small HDL particles deficient in SERPINA1 could increase cardiovascular disease risk in subjects with diabetes mellitus.

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