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
Por:
Ochoa-Guzman, A., Moreno-Macias, H., Guillen-Quintero, D., Chavez-Talavera, O., Ordonez-Sanchez, M. L., Segura-Kato, Y., Ortiz, V., Diaz-Diaz, E., Munoz-Hernandez, L., Garcia, A., Perez-Mendez, O., Zentella-Dehesa, A., Aguilar-Salinas, C. A., Tusie-Luna, M. T.
Publicada:
1 ago 2020
Resumen:
Purpose Type 2 diabetes (T2D) and low serum concentration of
high-density lipoprotein cholesterol (HDL-c) are common coexisting
metabolic disorders. ABCA1 variants have been shown to be associated to
these conditions. We sought to test the combined effect of two ABCA1
gene common variants, rs2422493 (- 565C > T) and rs9282541 (R230C) on
HDL-c levels and T2D risk. Methods Path analysis was conducted in 3,303
Mexican-mestizos to assess the specific contributions of rs2422493 and
rs9282541 ABCA1 variants, insulin resistance, waist-to-height ratio
(WHtR), and age on HDL-c levels and T2D risk. Participants were
classified into four groups according to their ABCA1 variants carrier
status: (i) the reference group carried wild type alleles for both ABCA1
variants (-/-), (ii) +/- were carriers of rs2422493 but non-carriers of
rs9282541, (iii) -/+ for carriers of rs9282541 but not carriers of
rs2422493 and (iv) carriers of minor alleles for both SNPs (+/+).
Principal components from two previous genome-wide association studies
were used to control for ethnicity. Results We identified significant
indirect effects on T2D risk mediated by HDL-c in groups -/+ and +/+
(beta = 0.04; p = 0.03 and beta = 0.06; p < 0.01, respectively) in
comparison to the -/- reference group. Low concentrations of HDL-c were
directly and significantly associated with increased T2D risk (beta =
-0.70; p < 0.01). WHtR, male gender, age, and insulin resistance were
also associated with T2D risk (p < 0.05). There was no significant
direct effect for any of the ABCA1 groups on T2D risk: p = 0.99, p =
0.58, and p = 0.91 for groups +/-, -/+, and +/+ respectively.
Conclusions The ABCA1 rs9282541 (R230C) allele is associated with T2D in
Mexicans through its effect on lowering HDL-c levels. This is the first
report demonstrating that HDL-c levels act as an intermediate factor
between an ABCA1 variant and T2D.
Filiaciones:
Ochoa-Guzman, A.:
Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Unit Mol Biol & Genom Med, Vasco de Quiroga 15,Belisario Dominguez Secc 16, Mexico City 14080, DF, Mexico
Moreno-Macias, H.:
Univ Autonoma Metropolitana, Mexico City, DF, Mexico
Guillen-Quintero, D.:
Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Unit Mol Biol & Genom Med, Vasco de Quiroga 15,Belisario Dominguez Secc 16, Mexico City 14080, DF, Mexico
Chavez-Talavera, O.:
Univ Nacl Autonoma Mexico, PECEM, Mexico City, DF, Mexico
Ordonez-Sanchez, M. L.:
Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Unit Mol Biol & Genom Med, Vasco de Quiroga 15,Belisario Dominguez Secc 16, Mexico City 14080, DF, Mexico
Segura-Kato, Y.:
Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Unit Mol Biol & Genom Med, Vasco de Quiroga 15,Belisario Dominguez Secc 16, Mexico City 14080, DF, Mexico
Ortiz, V.:
Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Physiol Nutr, Mexico City, DF, Mexico
Diaz-Diaz, E.:
Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Reprod Biol, Mexico City, DF, Mexico
Munoz-Hernandez, L.:
Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Res Unit Metab Dis, Mexico City, DF, Mexico
Garcia, A.:
Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Biochem, Mexico City, DF, Mexico
Perez-Mendez, O.:
Inst Nacl Cardiol Ignacio Chavez, Dept Mol Biol, Mexico City, DF, Mexico
Zentella-Dehesa, A.:
Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Biochem, Mexico City, DF, Mexico
Univ Nacl Autonoma Mexico, Inst Biomed Res, Mexico City, DF, Mexico
Aguilar-Salinas, C. A.:
Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Res Unit Metab Dis, Mexico City, DF, Mexico
Tusie-Luna, M. T.:
Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Unit Mol Biol & Genom Med, Vasco de Quiroga 15,Belisario Dominguez Secc 16, Mexico City 14080, DF, Mexico
Univ Nacl Autonoma Mexico, Inst Biomed Res, Mexico City, DF, Mexico
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