Contribution of common genetic variants to obesity and obesity-related traits in mexican children and adults.
BACKGROUND
Several studies have identified multiple obesity-associated loci mainly in European populations. However, their contribution to obesity in other ethnicities such as Mexicans is largely unknown. The aim of this study was to examine 26 obesity-associated single-nucleotide polymorphisms (SNP) in a sample of Mexican mestizos.


METHODS
9 SNPs in biological candidate genes showing replications (PPARG, ADRB3, ADRB2, LEPR, GNB3, UCP3, ADIPOQ, UCP2, and NR3C1), and 17 SNPs in or near genes associated with obesity in first, second and third wave GWAS (INSIG2, FTO, MC4R, TMEM18, FAIM2/BCDIN3, BDNF, SH2B1, GNPDA2, NEGR1, KCTD15, SEC16B/RASAL2, NPC1, SFRF10/ETV5, MAF, PRL, MTCH2, and PTER) were genotyped in 1,156 unrelated Mexican-Mestizos including 683 cases (441 obese class I/II and 242 obese class III) and 473 normal-weight controls. In a second stage we selected 12 of the SNPs showing nominal associations with obesity, to seek associations with quantitative obesity-related traits in 3 cohorts including 1,218 Mexican Mestizo children, 945 Mexican Mestizo adults, and 543 Indigenous Mexican adults.


RESULTS
After adjusting for age, sex and admixture, significant associations with obesity were found for 6 genes in the case-control study (ADIPOQ, FTO, TMEM18, INSIG2, FAIM2/BCDIN3 and BDNF). In addition, SH2B1 was associated only with class I/II obesity and MC4R only with class III obesity. SNPs located at or near FAIM2/BCDIN3, TMEM18, INSIG2, GNPDA2 and SEC16B/RASAL2 were significantly associated with BMI and/or WC in the combined analysis of Mexican-mestizo children and adults, and FTO locus was significantly associated with increased BMI in Indigenous Mexican populations.


CONCLUSIONS
Our findings replicate the association of 8 obesity-related SNPs with obesity risk in Mexican adults, and confirm the role of some of these SNPs in BMI in Mexican adults and children.
Unidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de Química, Universidad Nacional Autónoma de México-UNAM-Instituto Nacional de Medicina Genómica-INMEGEN, Mexico City, Mexico.
Paola
P
León-Mimila
Hugo
H
Villamil-Ramírez
Marisela
M
Villalobos-Comparán
Teresa
T
Villarreal-Molina
Sandra
S
Romero-Hidalgo
Blanca
B
López-Contreras
Roxana
R
Gutiérrez-Vidal
Joel
J
Vega-Badillo
Leonor
L
Jacobo-Albavera
Carlos
C
Posadas-Romeros
Adrián
A
Canizalez-Román
Blanca Del
BD
Río-Navarro
Francisco
F
Campos-Pérez
Victor
V
Acuña-Alonzo
Carlos
C
Aguilar-Salinas
Samuel
S
Canizales-Quinteros
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015992:Body Mass Index; D016022:Case-Control Studies; D002648:Child; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008800:Mexico / Q000453:epidemiology; D008875:Middle Aged; D009765:Obesity / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D055105:Waist Circumference; D055815:Young Adult