The FTO obesity gene. Genotyping and gene expression analysis in morbidly obese patients.
BACKGROUND
Obesity has emerged as one of the most serious public health concerns in the twenty-first century. the fat mass and obesity associated gene (FTO) has been found to contribute to the risk of obesity in humans. Our aims in this study were to investigate the association of rs9939609 single nucleotide polymorphism (SNP) of the FTO gene with different obesity-related parameters, to assess the FTO gene expression in subcutaneous and visceral adipose tissues from morbidly obese and its correlations with other adipocytokine gene expressions.


METHODS
The association between the rs9939609 FTO gene variant and obesity related parameters in 75 obese/morbidly obese adult patients and 180 subjects with body mass index (BMI) < 30 kg/m(2) (control group) was examined. Gene expression analyses: subcutaneous adipose tissue samples were obtained from 52 morbidly obese and five subjects with BMI < 30 kg/m(2). Visceral adipose tissue was also obtained from 35 morbidly obese patients. Weight, height, BMI, SBP, DBP, fasting glucose, lipid profile, proinsulin, insulin, leptin, and adiponectin (RIA) of patients were also obtained. Insulin resistance by HOMA(IR). rs9939609 of FTO genotyping using allele discrimination in real-time PCR. Genomic study of RNA extraction of adipose tissue and real-time PCR (RT-PCR) of adipocytokines and a housekeeping gene were quantified using TaqMan probes. Relative quantification was calculated using the DeltaDelta Ct formula.


RESULTS
The minor-(A) allele frequency of rs9939609 FTO gene in the whole population was 0.39. A strong association between this A allele and obesity was found, even after age-sex adjustment (p = 0.013). We found higher levels of FTO mRNA in subcutaneous adipose tissue from morbidly obese than in the control group (p = 0.021). FTO gene expression was lower in visceral than in subcutaneous adipose depot. However, this finding did not reach the level of statistical significance. A negative correlation between subcutaneous FTO gene expression and serum triglyceride levels and a positive correlation with leptin, perilipin, and visfatin gene expressions was found. In the visceral adipose tissue, these positive correlations were statistically significant only for perilipin.


CONCLUSIONS
Our results show: (1) A strong association between rs9939609 SNP of the FTO gene variant and obesity in Spanish morbidly obese adult patients; (2) positive correlations between FTO mRNA and leptin, perilipin, and visfatin gene expressions in subcutaneous adipose tissue; (3) FTO and perilipin gene expressions were positively correlated in visceral fat depot. Overall these results may suggest a role of FTO in the regulation of lipolysis as well as in total body fat rather in fat distribution patterns.
Department of Internal Medicine II, Hospital Clínico San Carlos, CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Cea Bermúdez 66, 5 G., 28003, Madrid, Spain.
Carina
C
Zabena
José L
JL
González-Sánchez
María T
MT
Martínez-Larrad
Antonio
A
Torres-García
Jesús
J
Alvarez-Fernández-Represa
Arturo
A
Corbatón-Anchuelo
Milagros
M
Pérez-Barba
Manuel
M
Serrano-Ríos
D054392:Adipokines / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000368:Aged; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D015992:Body Mass Index; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D050152:Intra-Abdominal Fat / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009767:Obesity, Morbid / Q000235:genetics* / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011506:Proteins / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D050151:Subcutaneous Fat / Q000378:metabolism
D054392:Adipokines; D011506:Proteins; D012333:RNA, Messenger; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human