TY - JOUR AU - Ruiz Díaz, María Stephany AU - Mena-Yi, Diana AU - Gómez- Camargo, Doris AU - Mora-García, Gustavo José PY - 2023/05/04 Y2 - 2024/03/28 TI - Interaction analysis of FTO and IRX3 genes with obesity and related metabolic disorders in an admixed Latin American population: a possible risk increases of body weight excess JF - Colombia Medica JA - Colomb Med VL - 53 IS - 2 SE - Original Articles DO - 10.25100/cm.v53i2.4874 UR - https://colombiamedica.univalle.edu.co/index.php/comedica/article/view/4874 SP - e2044874 AB - <p><strong>Background:</strong></p><p>Fat Mass and Obesity-related (FTO) has been one of the genes consistently related to&nbsp;common obesity. Single nucleotide polymorphisms (SNPs) in FTO have been linked&nbsp;with the IRX3 gene.</p><p><strong>Aim:</strong></p><p>This study was designed by testing the hypothesis that: i) common SNPs in FTO and&nbsp;IRX3 are associated with obesity and related disorders; ii) there is significant linkage&nbsp;disequilibrium between both genes.</p><p><strong>Methods:</strong></p><p>A cross-sectional study was carried out on the Colombian Caribbean Coast. Anthropometric and&nbsp;biochemical variables were measured, and obesity and metabolic disorders were diagnosed.&nbsp;Four SNPs were genotyped: 3 at FTO locus (rs17817449, rs8050136, rs9939609) and one at&nbsp;IRX3 locus (rs3751723). LD between these SNPs was estimated. A logistic regression model&nbsp;was applied to estimate associations.</p><p><strong>Results:</strong></p><p>A total of 792 subjects were included. FTO and IRX3 were not in LD (D’≤ 0.03; R2≤ 0.03). TT&nbsp;genotype (rs9939609) was found to be associated with waist circumference (p= 0.04; adj-p=0.01), and IRX3 SNP with Body Weight Excess (BWE) (OR= 1.06, adj-p= 0.03). One FTO-IRX3&nbsp;haplotype was associated with BWE (G-A-A-T, rs17817449-rs8050136-rs9939609-rs3751723;&nbsp;OR= 0.67, p= 0.04). The statistical significance of these relations continued after admixture&nbsp;adjustment for a three-hybrid population (p= 0.03).</p><p><strong>Conclusions:</strong></p><p>FTO was related to waist circumference, and IRX3 was associated with BWE in Latin American&nbsp;adults. This relation remained statistically significant after performing an adjustment for sex, age, and genetic&nbsp;ancestry. Despite these genes not being in LD, findings of a haplotype&nbsp;involving FTO-IRX3 suggest a gene-gene interaction associated with an increased risk of BWE.</p> ER -