RESUMO
OBJECTIVES: Obesity is a significant risk factor for a number of chronic diseases, including diabetes, cardiovascular diseases, and cancer. Obesity usually results from a combination of causes and contributing factors, including genetics and lifestyle choices. Many studies have shown an association of single nucleotide polymorphisms (SNPs) in the fat mass and obesity-associated (FTO) and the melanocortin-4 receptor (MC4R) genes with body mass index (BMI). Therefore, recognizing the main genes and their relevant genetic variants will aid prediction of obesity risk. The aim of our study was to investigate the frequency of rs9939609 and rs17782313 polymorphisms in FTO and MC4R genes in an Iranian population. METHODS: We enrolled 130 obese patients and 83 healthy weight controls and calculated their BMI. Genomic DNA was extracted from peripheral blood and the frequency of rs9939609 and rs17782313 polymorphisms in FTO and MC4R genes was determined using the tetra-primer amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). RESULTS: Significant associations were found between FTO rs9939609 and BMI. Where homozygous risk allele carriers (A-A) have significant higher odds ratio (OR) of being obese than individuals with normal BMI (OR = 6.927, p < 0.005, 95% confidence interval (CI): 3.48-13.78). No significant correlation between MC4R rs17782313 and obesity were observed when compared to healthy weight individuals. Although subjects with C-C genotype had higher odds of obesity (OR = 1.889, p = 0.077, 95%CI: 0.92-3.84). CONCLUSIONS: This study shows a relationship between FTO polymorphism and increased BMI, therefore, SNP in the FTO gene influence changes in BMI and can be considered a prognostic marker of obesity risk.
RESUMO
BACKGROUND: Heterogeneous breast cancer is the most common cause of cancer-related mortality. Obesity defined by BMI is a known major risk factor for breast cancer. OBJECTIVES: The purpose of this study was to explore the role of obesity related-polymorphisms rs9939609 Fat Mass and Obesity-associated (FTO) and rs17782313 MC4R in breast cancer development. MATERIALS AND METHODS: Matched peripheral blood serum was obtained from 64 breast cancer patients and 83 normal controls. Height and weight were measured to calculate BMI. All were genotyped for the SNPs rs9939609 and rs17782313 using a Tetra-primer ARMS-PCR method. For statistical analysis, the chi-square test and SPSS software were used. RESULTS: In subgroup analyses defined by BMI, FTO rs9939609 genotypes (TT/AA/AT) were significantly associated with the risk of breast cancer only in non-obese subjects (p < 0.005). TT genotypes of MC4R rs17782313 in non-obese and genotypes TT/CC in the overweight group were also statistically associated with breast cancer (p < 0.005). No significant associations between any variants and breast cancer risk were seen in obese subjects. CONCLUSION: Based on the absence of an association between obesity-related SNPs and breast cancer in obese subjects, it is proposed that weight gain in Iranian women will help prevent breast cancer risk. The result help for preparing and designing a safe and versatile recombinant drug in future.
