title: Gene polymorphisms and increased DNA damage in morbidly obese women.
abstract: Obesity is characterized by increased adipose tissue mass resulting from a chronic imbalance between energy intake and expenditure. Furthermore, there is a clearly defined relationship among fat mass expansion, chronic low-grade systemic inflammation and reactive oxygen species (ROS) generation; leading to ROS-related pathological events. In the past years, genome-wide association studies have generated convincing evidence associating genetic variation at multiple regions of the genome with traits that reflect obesity. Therefore, the present study aimed to evaluate the relationships among the gene polymorphisms ghrelin (GHRL-rs26802), ghrelin receptor (GHSR-rs572169), leptin (LEP-rs7799039), leptin receptor (LEPR-rs1137101) and fat mass and obesity-associated (FTO-rs9939609) and obesity. The relationships among these gene variants and the amount of DNA damage were also investigated. Three hundred Caucasian morbidly obese and 300 eutrophic (controls) women were recruited. In summary, the results demonstrated that the frequencies of the GHRL, GHSR, LEP and LEPR polymorphisms were not different between Brazilian white morbidly obese and eutrophic women. Exceptions were the AA-FTO genotype and allele A, which were significantly more frequent in obese women than in the controls (0.23% vs. 0.10%; 0.46 vs. 0.36, respectively), and the TT-FTO genotype and the T allele, which were less frequent in morbidly obese women (p<0.01). Furthermore, significant differences in the amount of genetic lesions associated with FTO variants were observed only in obese women. In conclusion, this study demonstrated that the analyzed SNPs were not closely associated with morbid obesity, suggesting they are not the major contributors to obesity. Therefore, our data indicated that these gene variants are not good biomarkers for predicting risk susceptibility for obesity, whereas ROS generated by the inflammatory status might be one of the causes of DNA damage in obese women, favoring genetically related diseases as obesity comorbidities.
authors.affiliation: Botucatu Medical School, UNESP-São Paulo State University, Brazil.
authors.forename: B C O
authors.initials: BC
authors.lastname: Luperini
authors.affiliation: Botucatu Medical School, UNESP-São Paulo State University, Brazil.
authors.forename: D C
authors.initials: DC
authors.lastname: Almeida
authors.affiliation: Botucatu Medical School, UNESP-São Paulo State University, Brazil.
authors.forename: M P
authors.initials: MP
authors.lastname: Porto
authors.affiliation: Botucatu Medical School, UNESP-São Paulo State University, Brazil.
authors.forename: J P C
authors.initials: JP
authors.lastname: Marcondes
authors.affiliation: Botucatu Medical School, UNESP-São Paulo State University, Brazil.
authors.forename: R P
authors.initials: RP
authors.lastname: Prado
authors.affiliation: Center of Gastroenterology and Surgery of Obesity, Piracicaba SP, Brazil.
authors.forename: I
authors.initials: I
authors.lastname: Rasera
authors.affiliation: Biosciences Institute, UNESP-São Paulo State University, Brazil.
authors.forename: M R M
authors.initials: MR
authors.lastname: Oliveira
authors.affiliation: Botucatu Medical School, UNESP-São Paulo State University, Brazil. Electronic address: dfavero@fmb.unesp.br.
authors.forename: D M F
authors.initials: DM
authors.lastname: Salvadori
mesh_terms: D000328:Adult; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D004249:DNA Damage; D005260:Female; D054439:Ghrelin / Q000235:genetics; D006801:Humans; D020738:Leptin / Q000235:genetics; D009767:Obesity, Morbid / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics; D054440:Receptors, Ghrelin / Q000235:genetics; D054411:Receptors, Leptin / Q000235:genetics
chemical_list: C515349:GHRL protein, human; D054439:Ghrelin; C515448:LEPR protein, human; D020738:Leptin; D011506:Proteins; D054440:Receptors, Ghrelin; D054411:Receptors, Leptin; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human
keywords: DNA damage; Gene polymorphisms; Morbidly obese women; Systemic inflammation