Associations of nicotidamide-N-methyltransferase, {FTO}, and {IRX}3 genetic variants with body mass index and resting energy expenditure in Mexican subjects

Banales Luna, Maciel y Figueroa Vega, Nicte y Marín Aragón, Carolina Ivet y Pérez Luque, Elva y Ibarra Reynoso, Lorena y Gallardo Blanco, Hugo L. y López Aguilar, Itzel y Malacara, Juan Manuel (2020) Associations of nicotidamide-N-methyltransferase, {FTO}, and {IRX}3 genetic variants with body mass index and resting energy expenditure in Mexican subjects. Scientific Reports, 10 (1). p. 11478. ISSN 2045-2322

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URL o página oficial: http://www.nature.com/articles/s41598-020-67832-7

Resumen

The enzyme nicotidamide‑n‑methyltransferase (nnMT) regulates adipose tissue energy expenditure through increasing nicotinamide adenosine dinucleotide (NAD+) content. nnMT methylates nicotinamide to N1-methylnicotidamide (MNA-1) using S-adenosyl methionine. The rs694539 NNMT polymorphism is associated with non-alcoholic steatohepatitis, and rs1941404 is associated with hyperlipidemia. The rs1421085 FTO is related to poor eating behaviors, and rs3751723 IRX3 is associated with obesity. To investigate the association of rs694539 and rs1941404 NNMT, rs140285 FTO and rs3751723 IRX3 polymorphisms with MNA-1 concentrations, resting energy expenditure (REE) and BMI, we included clinically healthy Mexican subjects 30 to 50 years old, 100 subjects (35 men/65 women) with BMI > 30 kg/m2 and 100 subjects (32 men/68 women) with BMI < 25 kg/m2. Glucose, lipid profile, insulin, leptin, acylated ghrelin, and MNA-1 (LC–MS) were quantified. Resting energy expenditure (Ree) was estimated using indirect calorimetry with a Fitmate instrument. Genotyping was performed using PCR–RFLP, and allelic discrimination was examined using TaqMan probes. MNA-1 concentrations and REE were significantly higher in obese subjects. Subjects with the rs694539AA NNMT genotype (recessive model) had lower weight, BMI, and Ree. BMI showed an association with HDL-C, triglycerides, MNA-1, acetylated ghrelin, leptin, insulin concentrations, HOMA-IR, REE, and rs1421085. Subjects with the TC or CC genotypes of rs1421085 FTO showed 6 kg and 2 units of BMI more than did those with the TT wild type. The CG of the rs1421085 and rs3751723 haplotypes was associated with BMI. These findings showed that BMI was strongly associated with REE, rs1421085 FTO and the CG rs1421085 FTO and rs3751723 IRX3 haplotypes. We used the GMDR approach in obesity phenotype to show the interaction of four Snps and metabolic variables.

Tipo de elemento:

Article

Palabras claves no controlados:

Alelos; Dioxigenasa dependiente de alfa-cetoglutarato FTO; Índice de masa corporal; Metabolismo energético; Estudios de asociación genética; Predisposición genética a enfermedades; Genotipo; Haplotipos; Proteínas homeodominio; Leptina; Nicotinamida N-metiltransferasa; Obesidad; Polimorfismo; Nucleótido único; Factores de transcripción

Materias:

CONACYT > Biología y Química
CONACYT > Medicina y Ciencias de la Salud

Divisiones:

Medicina

Usuario depositante:

Dr.C. Hugo Gallardo Blanco

Creadores:

Creador	Email	ORCID
Banales Luna, Maciel	NO ESPECIFICADO	NO ESPECIFICADO
Figueroa Vega, Nicte	NO ESPECIFICADO	NO ESPECIFICADO
Marín Aragón, Carolina Ivet	NO ESPECIFICADO	NO ESPECIFICADO
Pérez Luque, Elva	NO ESPECIFICADO	NO ESPECIFICADO
Ibarra Reynoso, Lorena	NO ESPECIFICADO	NO ESPECIFICADO
Gallardo Blanco, Hugo L.	hugo.gallardobl@uanl.edu.mx	orcid.org/0000-0002-7816-4967
López Aguilar, Itzel	NO ESPECIFICADO	NO ESPECIFICADO
Malacara, Juan Manuel	NO ESPECIFICADO	NO ESPECIFICADO