Linkage disequilibrium and haplotypes of the rs1042522, rs1625895, and rs1787862 markers of TP53 in patients with diffuse large B-cell lymphoma

The association of the rs1042522, rs17878362, and rs1625895 polymorphisms of TP53 with risk of non-Hodgkin’s lymphoma (NHL) has not been studied in full detail. NHL has many variants, and each individual polymorphism exerts only a minor effect, requiring the polymorphisms to be studied for particular histological subtypes of lymophomas and as components of haplotype groups. The objective of this work was to analyze the frequencies and linkage disequilibrium for rs1042522, rs1625895, and rs17878362 and their combined haplotype in patients with diffuse large B-cell lymphoma (DLBCL) and control subjects. Differences in linkage disequilibrium structure were observed for rs17878362, rs1042522, and rs1625895 in the Siberian population. The haplotype proved to be more informative than the individual TP53 polymorphisms in a case-control association analysis in DLBCL. Haplotype wArgG was associated with predisposition to DLBCL, while haplotypes wProG and dupProG were found to exert a protective effect. The effect of the haplotype at three TP53 polymorphisms was observed to vary depending on their homozygous or heterozygous state.     

Association of vitamin D receptor FokI and ApaI polymorphisms with lung cancer risk in Tunisian population

Many studies reported that Vitamin D Receptor (VDR) gene polymorphisms might influence the cancer risk due to their antiproliferative, antiangiogenic, and apoptotic effects. The aim of this study was to explore the genetic association of VDR polymorphisms with lung cancer risk in Tunisian population. The genotype and haplotype frequencies of four VDR polymorphisms, FokI (rs2228570), BsmI (rs1544410), ApaI (rs7975232) and TaqI (rs731236) were studied using polymerase chain reaction and restriction fragment length polymorphism analysis in 240 patients with lung cancer and 280 healthy controls. The distribution of genotype frequencies differed significantly between lung cancer subjects and controls (FokI P _adj  = 0.002; ApaI P _adj  = 0.013). Haplotype analyses revealed a significant association between G-A-C and A-C-T haplotypes and lung cancer risk (P _corr  = 0.0128, P _corr  = 0.008). When patients were stratified according to gender, age, and smoking, significant associations were detected with FokI and TaqI polymorphisms. We found a lack of association between BsmI, TaqI polymorphisms and lung cancer risk (P > 0.05). Only, the attributable proportion due to interaction and the synergic index for interaction between ApaI polymorphism and smoking were statistically significant (P _adj  = 0.74, 95 % CI = 0.38–1.20) and (P _adj  = 0.63, 95 % CI = 0.05–1.21), respectively. Both the additive interaction measures suggested the existence of a biological interaction between SNP ApaI, but not FokI, and smoking. The multiplicative interaction measure was not statistically significant (P > 0.05). This is the first study in Tunisia, which suggested that VDR FokI and ApaI polymorphisms might be risk factors for lung cancer development.     

Preliminary findings on the influence of FTO rs9939609 and MC4R rs17782313 polymorphisms on resting energy expenditure,leptin and thyrotropin levels in obese non-morbid premenopausal women

Given that leptin, ghrelin and thyrotropin play a major role in the regulation of resting energy expenditure (REE) and that the FTO rs9939609 and the MC4R rs17782313 polymorphisms have been proposed to affect energy homeostasis, we hypothesized that both polymorphisms are associated with REE and that these relationships can be mediated by leptin, ghrelin and thyrotropin in obesity. Therefore, the present study aimed to examine the relationships between FTO rs9939609 and the MC4R rs17782313 with REE, leptin, ghrelin and thyrotropin levels in obese women. The study comprised 77 obese (body mass index 34.0?±?2.8 kg/m²) women (age 36.7?±?7 years). We measured body composition by dual-energy X-ray absorptiometry and REE by indirect calorimetry. We analysed fasting leptin, ghrelin and thyrotropin levels and the ratio of leptin to fat mass was calculated. Genotype distributions of the polymorphisms did not deviate from Hardy–Weinberg expectations (P values >0.2). Women carrying the A allele of the FTO rs9939609 had lower REE (1,580?±?22 vs. 1,739?±?35 kcal/day, P?<?0.001) and higher leptin to fat mass ratio (1.33?±?0.05 vs. 1.13?±?0.08 ng/ml kg, P?<?0.05) and thyrotropin levels (1.93?±?0.10 vs. 1.53?±?0.16 μU/ml, P?<?0.05) regardless of age and body mass index. We found no significant influence of the MC4R rs17782313 on energy metabolism or biochemical variables. Our findings confirm that the A allele of the FTO rs9939609 is associated with lower REE and increased plasma leptin levels. We also found an association between the FTO rs9939609 and thyrotropin, suggesting the possible influence of FTO in the hypothalamic–pituitary–thyroid axis as a potential mechanism of the increased adiposity.     

A Pilot Study on the Contribution of Folate Gene Variants in the Cognitive Function of ADHD Probands

Genetic abnormalities in components important for the folate cycle confer risk for various disorders since adequate folate turnover is necessary for normal methylation, gene expression and chromosome structure. However, the system has rarely been studied in children diagnosed with attention deficit hyperactivity disorder (ADHD). We hypothesized that ADHD related cognitive deficit could be attributed to abnormalities in the folate cycle and explored functional single nucleotide polymorphisms in methylenetetrahydrofolate dehydrogenase (rs2236225), reduced folate carrier (rs1051266), and methylenetetrahydrofolate reductase (rs1801131 and rs1801133) in families with ADHD probands (N = 185) and ethnically matched controls (N = 216) recruited following the DSM-IV. After obtaining informed written consent for participation, peripheral blood was collected for genomic DNA isolation and PCR-based analysis of target sites. Data obtained was analyzed by UNPHASED. Interaction between sites was analyzed by the multi dimensionality reduction (MDR) program. Genotypic frequencies of the Indian population were strikingly different from other ethnic groups. rs1801133 “T” allele showed biased transmission in female probands (p < 0.05). Significant difference in genotypic frequencies for female probands was also noticed. rs1801131 and rs1801133 showed an association with low intelligence quotient (IQ). MDR analysis exhibited independent effects and contribution of these sites to IQ, thus indicating a role of these genes in ADHD related cognitive deficit.     

Meta-analysis of the relationship between single nucleotide polymorphism rs72689236 of caspase-3 and Kawasaki disease

Kawasaki disease is a pediatric systemic vasculitis of unknown etiology, for which a genetic influence is suspected. But whether single nucleotide polymorphism (SNP) of caspase-3 rs72689236 is associated with Kawasaki disease is controversial. The aim of our study is to assess the association between the SNP of caspase-3 and risk for Kawasaki disease. We searched PubMed, MEDLINE, EMBASE, Springer, Elsevier Science Direct, Cochrane Library Google scholar, CNKI (China National Knowledge Infrastructure, in Chinese) and Wanfang database (in Chinese) to identify studies investigating the association between rs72689236 polymorphism and Kawasaki disease occurrence. There were five eligible studies, which included 4,241 (case group 1,560; control group 2,681) participants in this meta-analysis. Pooled odds ratios (ORs) and 95 % confidence intervals (95 % CIs) were calculated in a fixed-effects model (the Mantel–Haenszel method) or a random-effects model (the DerSimonian and Laird method) when appropriate. Significant associations were found under the overall ORs for A-allele comparison (A vs. G, pooled OR 1.33, 95 % CI 1.21–1.46), AA versus GG comparison (pooled OR 1.64, 95 % CI 1.35–2.00), GA versus GG comparison (pooled OR 1.42, 95 % CI 1.24–1.63), recessive model (AA vs. GG + GA, pooled OR 1.37, 95 % CI 1.15–1.64) and dominant model (AA + GA vs. GG, pooled OR 1.47, 95 % CI 1.29–1.67). This meta-analysis suggested that SNP rs72689236 of caspase-3 might be associated with susceptibility of Kawasaki disease and the allele A might increase the risk of Kawasaki disease in Asian samples such as Japanese and Chinese. In addition, individual studies with large sample size are needed to further evaluate the associations in various ethnic populations.     

Polymorphism of DNA Repair Gene xrcc1 and Lung Cancer Risk

The current large-scale meta-analysis was performed to reach a reliable conclusion on the association between X-ray repair cross-complementing 1 (xrcc1) rs1799782 and the development of lung cancer. Studies that investigated the association between rs1799782 and lung cancer risk were identified by searching PubMed. We calculated odds ratio (OR) with corresponding 95 % confidence interval (CI) for Trp/Trp vs Arg/Arg, Trp/Trp + Arg/Trp vs Arg/Arg, and Trp/Trp vs Arg/Trp + Arg/Arg contrast models. Combining all 25 studies, we yielded three summary ORs: 1.07 (95 % CI 0.92–1.23) for Trp/Trp vs Arg/Arg, 0.93 (95 % CI 0.87–1.00) for Trp/Trp + Arg/Trp vs Arg/Arg, and 1.08 (95 % CI 0.94–1.25) for Trp/Trp vs Arg/Trp + Arg/Arg, suggesting rs1799782 was not associated with overall risk of lung cancer. Strikingly, a significantly deceased risk was found among Caucasian populations (Trp/Trp + Arg/Trp vs Arg/Arg, OR = 0.86, 95 % CI 0.76–0.97). This study confirms that xrcc1 rs1799782 may lower the risk of lung cancer among Caucasians.     

The common SNP (rs9939609) in the FTO gene modifies the association between obesity and high blood pressure in Chinese children

Previous studies have suggested that common variants in fat mass- and obesity-associated (FTO) gene are associated with body mass index (BMI) and the risk of obesity. Since obesity plays an important role in the etiology of high blood pressure (HBP), we aim to investigate the association between obesity and HBP in a population with different variants of the FTO gene. A total of 3,494 children (1,775 boys, 50.8 %) aged 6–18 years were recruited for measuring pubertal status, BMI and systolic and diastolic blood pressure. The single nucleotide polymorphism rs9939609 of the FTO gene was genotyped. The blood pressure levels increased by 1.4, 1.5 and 1.8 mmHg for systolic blood pressure and 0.8, 0.9 and 1.2 mmHg for diastolic blood pressure per 1-unit BMI increase in subjects carrying TT, TA and AA genotypes, respectively. After stratifying for FTO rs9939609 genotypes (TT, TA and AA), the odds ratios (95 % confidence intervals) of HBP in obese versus non-obese children were 4.26 (3.18–5.71), 5.13 (2.96–8.90) and 10.37 (1.59–67.43), respectively, with adjustment for age, gender and pubertal status. The FTO rs9939609 SNP modifies the effect of obesity on HBP in Chinese children, with obese ones carrying the AA homozygous genotype of the FTO rs9939609 having the highest risk of developing HBP.     

Association between CLPTM1L polymorphisms (rs402710 and rs401681) and lung cancer susceptibility: evidence from 27 case–control studies

Genome-wide association studies have identified two SNPs (rs402710 and rs401681) of CLPTM1L at chromosome 5p15.33 as a new lung cancer (LC) susceptibility locus in populations of European descent. Since then, the relationship between these SNPs and LC has been reported in various ethnic groups; however, these studies have yielded inconsistent results. To investigate this inconsistency, we performed a meta-analysis of 27 studies involving a total of 60,828 cases and 109,135 controls for the two polymorphisms to evaluate its effect on genetic susceptibility for LC. An overall random-effects per-allele odds ratio of 1.14 (95 % CI 1.11–1.16, P < 10^?5) and 1.15 (95 % CI 1.12–1.19, P < 10^?5) was found for the rs401681 and rs402710 polymorphism, respectively. Significant results were also observed for under dominant and recessive genetic models. After stratified by ethnicity, significant associations were found among Caucasians and East Asians. In the subgroup analysis by sample size, significantly increased risks were found for these polymorphisms in all genetic models. In addition, we find both rs402710 and rs401681 conferred significantly greater risks for adenocarcinoma and squamous cell carcinoma when stratified by histological type of tumors. Furthermore, associations of these polymorphisms with LC risk were observed among current smokers and former smokers, as well as never smokers. Our findings demonstrated that rs402710 and rs401681 are risk-conferring factors for the development of lung cancer.     

Association of a common rs9939609 variant in the fat mass and obesity-associated (<Emphasis Type="Italic">FTO</Emphasis>) gene with obesity and metabolic phenotypes in a Taiwanese population: a replication study

It is a key challenge to conduct reproducibility in genetic research, especially association studies in obesity. While susceptibility of a single-nucleotide polymorphism (SNP), rs9939609, in the fat mass and obesity-associated (FTO) gene to obesity has been reported in various populations, data from Asians is less conclusive. This replication study was carried out to test whether the FTO rs9939609 SNP is a predictive factor for obesity and obesity-related metabolic traits in a Taiwanese population. A total of 1188 Taiwanese subjects were recruited for this study. The FTO rs9939609 SNP was genotyped by the Taqman assay. Obesity-related metabolic traits such as triglyceride, waist circumference, systolic and diastolic blood pressure, total cholesterol, creatinine, alanine aminotransferase and fasting glucose were measured. Our data revealed that the FTOrs9939609 SNP exhibited a significant association with obesity (BMI \(\geqq \) 30 kg/m ²) among the subjects (P= 0.026). However, the FTO rs9939609 SNP did not exhibit any significant association with obesity-related metabolic traits among the subjects. Our results indicated that the FTO rs9939609 SNP may be linked with the risk of obesity in Taiwanese subjects.     

Association Between Single Nucleotide Polymorphisms of Sterol Regulatory Element Binding Protein-2 and Liver X Receptor α Gene and Risk of Polycystic Ovary Syndrome in a Chinese Han Population

To investigate associations of single nucleotide polymorphisms (SNPs) rs2228314 of sterol regulatory element-binding protein-2 (SREBP-2) or rs11039155 of liver X receptor α (LXRα) with susceptibility to polycystic ovary syndrome (PCOS) in a Chinese Han population. SREBP-2 rs2228314 and LXRα rs11039155 polymorphisms were genotyped in patients with PCOS and age- and sex-matched PCOS-free controls from a Chinese Han population. A total of 605 patients with PCOS and 615 controls were recruited in this study. We found that GC and CC genotypes of rs2228314, and variant C, were associated with a significantly increased risk of PCOS. In addition, GA and AA genotypes of rs11039155, as well as variant A, were also associated with a significantly increased risk of PCOS. Our results showed that SREBP-2 rs2228314 G to C change and variant C genotype as well as LXRα rs11039155 G to A change and variant A may contribute to PCOS in Chinese Han population.     

Common polymorphisms of calpain-10 and the risk of polycystic ovary syndrome in Tunisian population: a case–control study

Recent studies have suggested that calpain-10 (CAPN10) gene polymorphisms play a role in the susceptibility to polycystic ovary syndrome (PCOS). The aim of the present study was to evaluate the possible association between three single nucleotide polymorphisms (SNPs) in CAPN10 gene: UCSNP-43 (rs3792267), UCSNP-19 (rs3842570), and UCSNP-63 (rs5030952) and PCOS in Tunisian cases and control women. Study subjects included 127 women with PCOS (mean age 29.8 ± 4.7 year) and 150 healthy women (mean age 33.5 ± 5.6 year). CAPN10 genotyping was carried-out by direct PCR and PCR–RFLP. Linkage disequilibrium pattern in the genomic region explored was determined by HAPLOVIEW 4.2 while reconstruction of haplotypes was done using PHASE 2.1. The phylogenetic distribution of haplotypes in the population was determined by ARLEQUIN 2.000. Six haplotypes were observed. None of SNPs associated with PCOS or its components while the haplotype H4 associated with the phenotype PCOS-obese (P < 0.025). Moreover the pair of haplotypes H1/H4 strongly associated with high blood-pressure (OR = 14.4, P < 0.012). This work confirms the association of CAPN10 gene with metabolic components in PCOS and highlights the role of haplotypes as strong and efficient genetic markers.     

A prepared anti-MSTN polyclonal antibody reverses insulin resistance of diet-induced obese rats via regulation of PI3K/Akt/mTOR&FoxO1 signal pathways

Suppression of myostatin (MSTN) is associated with skeletal muscle atrophy and insulin resistance. However, the mechanisms by which MSTN regulates insulin resistance are not well known. We have explored the signaling pathways through which MSTN regulates insulin resistance in diet-induced obese rats using a polyclonal antibody for MSTN. The anti-MSTN polyclonal antibody significantly improved insulin resistance and whole-body insulin sensitivity, decreased MSTN protein expression in muscle samples by 39 % in diet-induced obese rats. Furthermore, the anti-MSTN polyclonal antibody significantly enhanced PI3K activity (140 %), Akt phosphorylation (86 %), GLUT4 protein expression (23 %), the phosphorylation of mTOR (21 %), and inhibited the phosphorylation of FoxO1 (57 %), but did not affect the phosphorylation of GSK-3β. Thus, suppression of MSTN by the anti-MSTN polyclonal antibody reverses insulin resistance of diet-induced obesity via MSTN/PI3K/Akt/mTOR and MSTN/PI3K/Akt/FoxO1 signaling pathways.     

Analysis on the association between PPARα/γ polymorphisms and lipoprotein(a) in a Chinese Han population

Lipoprotein(a) [Lp(a)], a low-density lipoprotein-like particle, is recognized as an independent risk factor for atherosclerosis, cardiovascular diseases, and diabetic vascular diseases. Our recent studies revealed that the single nucleotide polymorphisms (SNPs) of peroxisome proliferator-activated receptors (PPARα/δ/γ) gene are involved in the regulation of lipid storage and metabolism. In order to investigate the relationships between the SNPs of PPARα/γ gene and plasma levels of Lp(a), 644 participants were randomly selected from Chinese Han population in the present study. As the results shown, Lp(a) was significantly associated with L162V (rs1800206) in PPARα. Compared with those subjects with widetype (LL), significantly higher Lp(a) concentration was determined in the individuals with mutant (LV + VV) (mean difference: 49.07 mg/l, 95 % CI 23.32–74.82 mg/l, p = 0.0002). Moreover, with generalized multifactor dimensionality reduction analysis, our present results indicated that there was a significant association between plasma Lp(a) level and gene–gene interaction among the polymorphisms rs1800206, rs135539 in PPARα and rs10865710, rs1805192, and rs4684847 in PPARγ. Therefore, our presented study indicated that PPARα/γ polymorphisms should be involved in the regulation of plasma Lp(a) in independently and/or in an interactive manner, suggesting that PPARα/γ gene may influence the risk of hypertension, cardiovascular diseases, and dyslipidemia by regulating Lp(a) level.     

Combined effects of the BDNF rs6265 (Val66Met) polymorphism and environment risk factors on psoriasis vulgaris

Smoking, alcohol consumption and higher body mass index (BMI) are well established risk factors for psoriasis and also associated with the clinical traits of the disease. And the genetic influences on these three risk factors indeed exist. Previously studies have demonstrated these risk factors related genetic variants may also play a role in the development of risk factors-related diseases. Then we performed a hospital-based study in order to evaluate the combined effect of the risk factors and their related polymorphism rs6265 in brain-derived neurotrophic factor (BDNF) gene on psoriasis vulgaris (PV) risk and clinic traits. The case–control study involved 660 subjects including 345 cases and 315 controls in Chinese Han population. The variant of rs6265 was typed by SNaPshot Multiplex Kit (Applied Biosystems Co., USA). We confirmed that higher BMI (≥25), smoking and alcohol consumption were risk factors for PV, and the estimated ORs were 1.63(95 % confidence interval (CI); 1.12–2.37), 2.09(95 % CI; 1.44–3.03) and 1.65(95 % CI; 1.15–2.37) respectively. Genotype and allele distributions did not differ significantly between case and control. However, we found combined effect of rs6265 genotype (GG) and higher BMI (≥25) increased risk of PV (OR = 2.09; 95 % CI, 1.02–4.28; P < 0.05; adjusted OR = 3.19; 95 % CI, 1.37–7.45; P < 0.05) and clinically severity of PV (OR = 2.71; 95 % CI, 1.09–6.72; P < 0.05; adjusted OR = 1.25; 95 % CI, 1.10–1.40; P < 0.05). But none such significant combined effect was observed between others genotype (AA and AG) and other risk factors. In conclusions, the combined effect of BDNF rs6265 genotype (GG) and higher BMI may increases the risk and clinical severity of PV in Chinese Han population.     

Association of resistin polymorphisms with resistin levels and lipid profile in children

Previous research has found a correlation between resistin and lipid level variations. Polymorphisms in the resistin gene (RETN) could be involved in this relationship, but the results of the different studies are contradictory. The aim of this study was to examine the association between resistin and lipid levels, and to determine whether resistin polymorphisms are associated with resistin levels and lipid profile in prepubertal children and adolescents. The single nucleotide polymorphisms (SNPs) rs1862513 and rs10401670 were analyzed in 442 randomly selected 6- to 8-year-old children and 827 children aged 12–16 years. Anthropometric data were recorded. Lipid profile was determined using standard methods. Serum resistin levels were measured using a multiplexed bead immunoassay. Resistin polymorphisms were determined by TaqMan^® allelic discrimination assays. A relationship was found between serum levels of resistin and the SNP rs10401670 in 6- to 8-year-old boys. SNP rs10401670 was also related to TC and LDL-cholesterol in 12- to 16-year-old boys and to HDL-C in 12- to 16-year-old girls. SNP rs1862513 was not related to any of the studied variables. Serum resistin levels were significantly and negatively associated with ApoAI levels in 12- to 16-year-old girls. A SNP in the 3′UTR region of RETN (rs10401670) is associated with resistin levels and lipid profile in children, showing different associations depending on age and gender.     

Single-nucleotide polymorphism associations in common with immune responses to measles and rubella vaccines

Single-nucleotide polymorphisms (SNPs) in candidate immune response genes were evaluated for associations with measles- and rubella-specific neutralizing antibodies, interferon (IFN)-γ, and interleukin (IL)-6 secretion in two separate association analyses in a cohort of healthy immunized subjects. We identified six SNP associations shared between the measles-specific and rubella-specific immune responses, specifically neutralizing antibody titers (DDX58), secreted IL-6 (IL10RB, IL12B), and secreted IFN-γ (IFNAR2, TLR4). An intronic SNP (rs669260) in the antiviral innate immune receptor gene, DDX58, was significantly associated with increased neutralizing antibody titers for both measles and rubella viral antigens post-MMR vaccination (p values 0.02 and 0.0002, respectively). Significant associations were also found between IL10RB (rs2284552; measles study p value 0.006, rubella study p value 0.00008) and IL12B (rs2546893; measles study p value 0.005, rubella study p value 0.03) gene polymorphisms and variations in both measles- and rubella virus-specific IL-6 responses. We also identified associations between individual SNPs in the IFNAR2 and TLR4 genes that were associated with IFN-γ secretion for both measles and rubella vaccine-specific immune responses. These results are the first to indicate that there are SNP associations in common across measles and rubella vaccine immune responses and that SNPs from multiple genes involved in innate and adaptive immune response regulation may contribute to the overall human antiviral response.     

Association between Fok I vitamin D receptor gene (VDR) polymorphism and impulsivity in alcohol-dependent patients

Vitamin D appears to have an important role in the modulation of the central nervous system. Vitamin D exerts its biological effects through its interaction with the vitamin D receptor (VDR). Located on chromosome 12 (12q13.1), the VDR gene has many different polymorphisms. Some of them are known to affect the VDR function, such as FokI (rs2228570, T/C) single nucleotide polymorphism. We aimed to explore a potential relationship between FokI VDR polymorphism and impulsiveness in alcohol-dependent (AD) patients. The study population consisted of 148 patients diagnosed with alcohol dependence (DSM-IV criteria) and 212 healthy controls. DNA was extracted from whole blood samples using the standard procedure. Genotypes were analyzed using a real-time PCR method. We found that FokI VDR gene polymorphism was associated with impulsivity [Barratt Impulsiveness Scale (BIS)-11 total score; P = 0.014], and with attentional impulsivity (BIS-11 subscale; P = 0.002) in the male AD patients. Our results suggest that CC FokI genotype of the VDR gene is associated with a higher level of impulsivity in these patients. This finding supports the hypothesis that impulsiveness, which significantly contributes to development of alcohol dependence, has a genetic background.     

Interaction between obesity-related genes, FTO and MC4R, associated to an increase of breast cancer risk

Breast cancer (BC) is a complex disease and obesity is a well-known risk factor for its development, especially after menopause. Several studies have shown Single Nucleotide Polymorphisms (SNPs) linked to overweight and obesity, such as: rs1121980 (T/C) and rs9939609 (A/T) in Fat Mass and Obesity Associated gene (FTO) and rs17782313 (T/C) in Melanocortin 4 Receptor gene (MC4R). Thus, we aimed to investigate the association between these obesity-related SNPs and BC risk. One hundred BC patients and 148 healthy women from Santa Catarina, Brazil entered the study. SNPs were genotyped using Taqman assays. For statistical analyses SNPStats and SPSS softwares were used. Association analyses were performed by logistic regression and were adjusted for age and Body mass index (BMI). Multiple SNPs inheritance models (log-additive, dominant, recessive, codominant) were performed to determine odds ratios (ORs), assuming 95 % confidence interval (CI) and P value = 0.05 as the significance limit. When analyzed alone, FTO rs1121980 and rs9939609 did not show significant associations with BC development, however MC4R rs17782313 showed increased risk for BC even after adjustments (P-value = 0.032). Interestingly, the interaction of FTO and MC4R polymorphisms showed a powerful association with BC. We observed a 4.59-fold increased risk for woman who have the allele combination C/T/C (FTO rs1121980/FTO rs9939609/MC4R rs17782313) (P-value = 0.0011, adjusted for age and BMI). We found important and unpublished associations between these obesity-related genes and BC risk. These associations seem to be independent of their effect on BMI, indicating a direct role of the interaction between FTO and MC4R polymorphisms in BC development.