The association of the fat mass and obesity-associated gene (FTO) rs9939609 polymorphism and the severe obesity in a Brazilian population

Abstract

Background:

Obesity occurs due to the interaction between the genetic background and environmental factors, including an increased food intake and a sedentary lifestyle. Nowadays, it is clear that there is a specific circuit, called leptin-melanocortin pathway, which stimulates and suppresses food intake and energy expenditure. Therefore, the aim of this study was to evaluate the influence of genetic variants related to appetite regulation and energy expenditure on severe obesity susceptibility and metabolic phenotypes in a Brazilian cohort.

Material and methods:

A total of 490 participants were selected (298 severely obese subjects and 192 normal-weight individuals). Genomic DNA was extracted and polymorphisms in protein related to agouti (AGRP; rs5030980), ghrelin (GHRL; rs696217), neuropeptide Y (NPY; rs535870237), melanocortin 4 receptor (MC4R; rs17782313), brain-derived neurotrophic factor (BDNF; rs4074134) and fat mass and obesity-associated (FTO; rs9939609) genes were genotyped using TaqMan® probes. Demographic, anthropometric, biochemical and blood pressure parameters were obtained from the participants.

Results:

Our results showed that FTO rs9939609 was associated with severe obesity susceptibility. This polymorphism was also related to body weight, body mass index (BMI), waist to weight ratio (WWR) and inverted BMI. Individuals carrying the mutant allele (A) showed higher levels of BMI as well as lower values of WWR and inverted BMI.

Conclusion:

This study showed that FTO rs9939609 polymorphism plays a significant role in predisposing severe obesity in a Brazilian population.

Keywords:

• leptin-melanocortin pathway
• FTO
• obesity
• polymorphisms
• hypothalamus

Acknowledgments

The author would like to thank the participants who kindly agreed to join in this study. We are grateful to Nereida Proença da Fonseca for her great technical assistance and Rosimere Lima for her excellent work with patients in GRACO. This work was supported by Oswaldo Cruz Foundation (FIOCRUZ, Rio de Janeiro - Brazil), National Council for Scientific and Technological Development (CNPq) and Coordination for the Improvement of Higher Education Personnel (CAPES).

Disclosure

The authors report no conflicts of interest in this work.

Supplementary materials

PCR procedure for NPY polymorphism

The region was amplified using custom designed primers (forward: 5’-GCGGCGAGGAAGCTCCATAA-3’; reverse: 5’-CCTAGACAGACGGGTCGTAG-3’). PCR reactions (25 µl) consisted of 20–50 ng of DNA, 1 unit of Taq DNA polymerase (Biotools B&M Labs. S.A, Madrid, Spain), 0.2 mmol/L of each dNTP, 2 mmol/L MgCl₂ and 0.3 pmoles of each primer. The thermocycling condition started with an initial denaturation at 95 ºC for 10 min, followed by 30 cycles of 94 ºC for 1 min; 60 ºC for 1 min; 72 ºC for 1 min; and a final extension step of 72 ºC for 10 min. The 159 bp amplified fragment of NPY gene was analyzed on a 15% polyacrylamide gel.

Table S1 Phenotypic characteristics of study population

Table S2 Association of polymorphisms studied and anthropometric, biochemical and blood pressure variables