MON-092 Role of Genetic Variants of NNMT rs694539 and rs1941404, FTO rs1421085 and Irx3 rs3751723 Polymorphisms on Resting Energy Expenditure and BMI

In obesity the NNMTrs694539 polymorphism associates with cardiovascular damage and nonalcoholic steatohepatitis, and rs1941404 with hyperlipidemia.NNMT (Nicotidamide-N-methyltransferase) is a regulator of adiposity and energy expenditure correlating with BMIand energy metabolism. FTOrs1421085 polymorphism regulates food behavior, and IRX3rs3751723 is associated with obesity risk.Resting energy expenditure (REE) is an essential component of obesity. To evaluate the role of NNMTrs694539 and rs1941404,and FTOrs1421085 and IRX3rs3751723 polymorphisms on REEand BMI. We recruited 200 healthy subjects 30 to 50 years of age, 100 non-obese (BMI 18.5-29.5) and 100 obese (BMI ≥30 kg/m(2)). and REE evaluated by indirect calorimetry. A fasting blood sample was obtained for metabolites and DNA extraction. Leptin and insulin were quantified. MNA-1 was measured by LC-MS. The NNMTrs694539, rs1941404, FTOrs1421085, and IRX3rs3751723 polymorphisms were genotyped by PCR-RFLP and Taqman allelic discrimination respectively. MNA-1 concentrations and REE were higher in obese subjects. REE correlated with BMI, (p < 0.00001), insulin (p=0.001) andHOMA-IR (p=0.0004). The plasma MNA-1 correlated negatively with HOMA-IR in obese subjects (p=0.042). The rs694539AA genotype frequency was significantly higher in lean subjects. The NNMTrs1941404, and IRX3 rs3751723 polymorphisms was not different in allelic or genotypes frequencies in both groups. The risk allele frequency of FTOrs1421085 was different between groups (p=0.049; OR=1.76). Carriers of one or two risk alleles had more weight 6 kg or 2 BMI units than subjects with WT genotype. Under recessive model carriers of rs694539 AA genotype had lower weight, BMI, and REE than those with GG and AG genotypes, andcarriers of rs1941404GG genotype had marginally higher BMI, leptin, and MNA. The TG haplotype of rs1421085 and rs3751723 were associated with BMI adjusted by gender and age (coefficient -3.41±1.41, p=0.017). REE and MNA-1 were significant higher in obese subjects. Carriers of rs694539 AA genotype had lower weight, BMI, REE. The risk allele frequency of FTOrs1421085 was marginally different (p=0.049; OR=1.76) among groups. The carriers of one or two risk allele had 6 kg and 2 BMI units more than wild type genotype subjects. TG haplotype of rs1421085 and rs3751723 was associated with BMI. Support: CONACYT, and CIFOREA-UG.