title: Gender-Dependent Association of FTO Polymorphisms with Body Mass Index in Mexicans.
abstract: To evaluate the associations between six single-nucleotide polymorphisms (SNPs) in intron 1 of FTO and body mass index (BMI), a case-control association study of 2314 unrelated Mexican-Mestizo adult subjects was performed. The association between each SNP and BMI was tested using logistic and linear regression adjusted for age, gender, and ancestry and assuming additive, recessive, and dominant effects of the minor allele. Association analysis after BMI stratification showed that all five FTO SNPs (rs1121980, rs17817449, rs3751812, rs9930506, and rs17817449), were significantly associated with obesity class II/III under an additive model (P<0.05). Interestingly, we also documented a genetic model-dependent influence of gender on the effect of FTO variants on increased BMI. Two SNPs were specifically associated in males under a dominant model, while the remainder were associated with females under additive and recessive models (P<0.05). The SNP rs9930506 showed the highest increased in obesity risk in females (odds ratio = 4.4). Linear regression using BMI as a continuous trait also revealed differential FTO SNP contributions. Homozygous individuals for the risk alleles of rs17817449, rs3751812, and rs9930506 were on average 2.18 kg/m(2) heavier than homozygous for the wild-type alleles; rs1121980 and rs8044769 showed significant but less-strong effects on BMI (1.54 kg/m(2) and 0.9 kg/m(2), respectively). Remarkably, rs9930506 also exhibited positive interactions with age and BMI in a gender-dependent manner. Women carrying the minor allele of this variant have a significant increase in BMI by year (0.42 kg/m(2), P = 1.17 x 10(-10)). Linear regression haplotype analysis under an additive model, confirmed that the TGTGC haplotype harboring all five minor alleles, increased the BMI of carriers by 2.36 kg/m(2) (P = 1.15 x 10(-5)). Our data suggest that FTO SNPs make differential contributions to obesity risk and support the hypothesis that gender differences in the mechanisms involving these variants may contribute to disease development.
authors.affiliation: Laboratorio de Immunogenómica y Enfermedades Metabólicas, Instituto Nacional de Medicina Genómica, Secretaría de Salud, Mexico City, Mexico.
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Saldaña-Alvarez
authors.affiliation: Laboratorio de Immunogenómica y Enfermedades Metabólicas, Instituto Nacional de Medicina Genómica, Secretaría de Salud, Mexico City, Mexico.|Programa de Ciencias Genómicas, Universidad Autónoma de la Cd. de México, Mexico City, Mexico.
authors.forename: María Guadalupe
authors.initials: MG
authors.lastname: Salas-Martínez
authors.affiliation: Laboratorio de Immunogenómica y Enfermedades Metabólicas, Instituto Nacional de Medicina Genómica, Secretaría de Salud, Mexico City, Mexico.
authors.forename: Humberto
authors.initials: H
authors.lastname: García-Ortiz
authors.affiliation: Hospital Regional 1° de Octubre, ISSSTE, Mexico City, Mexico.
authors.forename: Angélica
authors.initials: A
authors.lastname: Luckie-Duque
authors.affiliation: Clínica de Diagnóstico Autorizado, ISSSTE, Mexico City, Mexico.
authors.forename: Gustavo
authors.initials: G
authors.lastname: García-Cárdenas
authors.affiliation: Hospital Regional Adolfo López Mateos, ISSSTE, Mexico City, Mexico.
authors.forename: Hermenegildo
authors.initials: H
authors.lastname: Vicenteño-Ayala
authors.affiliation: Laboratorio de Immunogenómica y Enfermedades Metabólicas, Instituto Nacional de Medicina Genómica, Secretaría de Salud, Mexico City, Mexico.
authors.forename: Emilio J
authors.initials: EJ
authors.lastname: Cordova
authors.affiliation: Centro Nacional para la Salud de la Infancia y la Adolescencia, Secretaría de Salud, Mexico City, Mexico.
authors.forename: Marcelino
authors.initials: M
authors.lastname: Esparza-Aguilar
authors.affiliation: Laboratorio de Immunogenómica y Enfermedades Metabólicas, Instituto Nacional de Medicina Genómica, Secretaría de Salud, Mexico City, Mexico.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Contreras-Cubas
authors.affiliation: Instituto Nacional de Medicina Genómica, Secretaría de Salud, Mexico City, Mexico.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Carnevale
authors.affiliation: Instituto Nacional de Pediatría, Secretaría de Salud, Mexico City, Mexico.
authors.forename: Margarita
authors.initials: M
authors.lastname: Chávez-Saldaña
authors.affiliation: Laboratorio de Immunogenómica y Enfermedades Metabólicas, Instituto Nacional de Medicina Genómica, Secretaría de Salud, Mexico City, Mexico.|Programa de Ciencias Genómicas, Universidad Autónoma de la Cd. de México, Mexico City, Mexico.
authors.forename: Lorena
authors.initials: L
authors.lastname: Orozco
mesh_terms: D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D015992:Body Mass Index; D005260:Female; D005787:Gene Frequency; D006801:Humans; D008297:Male; D008800:Mexico; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*; D012737:Sex Factors
chemical_list: D011506:Proteins; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human