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.     

Asociación de polimorfismos en el gen FTO con la obesidad mórbida en la población extremeña

ObjectiveTo select individuals whose morbid obesity can be attributed mainly to their individual genetic profile. After excluding patients with potential monogenic syndromes or diseases associated with obesity, we evaluated the association of the single nucleotide polymorphisms (SNPs) rs1861868 and rs9939609 of the fat-mass and obesity-associated FTO gene with an inherited predisposition to morbid obesity.Patients and methodsWe evaluated 270 patients with morbid obesity and onset before the age of 14 years and selected 194 due to their phenotypes and family history; 289 control individuals were included. The rs1861868 and rs9939609 variants, located in the FTO gene, were genotyped. Genotype and haplotype frequencies were compared between cases and controls.ResultsThe A allele of rs9939609 was associated with severe obesity starting in childhood among the Spanish population. The rs1861868 G/rs9939609 A haplotype of the FTO gene was also significantly associated with severe obesity in our population, with an odds ratio of 3.03 (95% confidence interval, 1.74–5.27).ConclusionAnalysis of the genetic basis of obesity requires rigorous selection of cases. In this study, the association of the rs9939609 SNP with obesity widely described in distinct populations was confirmed among overweight Spanish children. Genotyping rs1861868 allowed us to identify the first risk haplotype in the FTO gene, which is located in the adjacent haplotype block containing rs9939609. In-depth study of the variability of the FTO gene is essential to define its deleterious capacity.     

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.     

Common variant (rs9939609) in the<Emphasis Type="Italic"> FTO</Emphasis> gene is associated with metabolic syndrome

Recent genome-wide association studies have showed that common variant (rs9939609) in fat mass and obesity associated (FTO) gene was significantly associated with type 2 diabetes through an effect on human body mass index/obesity. Further studies have suggested that this variant was also involved in the development of metabolic syndrome (MetS). However, the results have been inconsistent. In this study, we performed a meta-analysis to clarify the association between rs9939609 polymorphism and the risk of MetS. Published literature from PubMed, EMBASE and other databases were searched. All studies assessing the association between rs9939609 polymorphism and the risk of MetS were identified. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated using fixed-effects model. Thirteen studies (8,370 cases and 23,156 controls) using NCEP ATPIII criteria for MetS were pooled with a meta-analysis. The overall result showed that there was a statistically significant association between rs9939609 polymorphism and MetS risk (OR = 1.11, 95% CI = 1.06–1.17). Subgroup analysis based on ethnicity showed that effect size was only statistically significant in Europeans (OR = 1.11, 95% CI = 1.05–1.16). Eight studies (1,256 cases and 2,551 controls) using IDF criteria for MetS were pooled with a meta-analysis. The overall analysis suggested that rs9939609 polymorphism was significantly associated with MetS risk (OR = 1.32, 95% CI = 1.13–1.54). Subgroup analysis stratified by ethnicity suggested that effect size was only statistically significant in Asians (OR = 1.33, 95% CI = 1.10–1.61). Our results suggested that FTO rs9939609 polymorphism was significantly associated with the increased risk of MetS in European and Asian populations. Mechanistic investigation is also needed to clarify the effect of FTO gene in the predisposition to MetS.     

The association between fat mass and obesity-associated (FTO) genotype and serum vitamin D level in breast cancer patients

The preventive effect of vitamin D against breast cancer can be influenced by gene polymorphisms. This study aimed to investigate the association between serum level of 25(OH) vitamin D and FTO genotype in breast cancer patients. A cross-sectional study was carried out on 180 newly diagnosed patients with breast cancer in Tehran, Iran. The blood samples were collected from the participants in order to assess the FTO gene rs9939609 polymorphism by the tetra-primer amplification refractory mutation system (Tetra-ARMS) PCR method. The serum level of 25(OH) vitamin D was measured using the direct competitive enzyme-linked immunosorbent assay (ELISA) method. The association between vitamin D and the FTO genotype in patients with breast cancer was assessed after adjustment for cofounders. The frequency of TT, AT and AA genotypes in the breast cancer patients were 43% (n = 77), 49% (n = 89) and 8% (n = 14), respectively. All patients with higher than 40 ng/dl of serum 25(OH) vitamin D had one or two copies of FTO rs9939609 risk allele (p = 0.019). No linear association was found between the number of FTO risk allele and the level of serum vitamin D. All patients with high serum level of 25(OH) vitamin D had one or two copies of FTO rs9939609 risk allele. FTO gene polymorphisms may counteract the beneficial effects of vitamin D in breast cancer prevention. Further studies can help to better understand the genetic factors predisposing to breast cancer and their effect on the association between vitamin D and breast cancer.     

The Common Variant in the FTO Gene Did Not Modify the Effect of Lifestyle Changes on Body Weight: The Finnish Diabetes Prevention Study

The common single‐nucleotide polymorphism in the FTO (fat mass and obesity associated) gene is consistently associated with an increased risk of obesity. However, the knowledge of a potential modifying effect of the FTO gene on changes in body weight achieved by lifestyle intervention is limited. We examined whether the FTO gene variant (rs9939609, T/A) is associated with body weight and BMI and long‐term weight changes in the Finnish Diabetes Prevention Study (DPS). Altogether, 522 (aged 40–65 years; BMI ≥25 kg/m²) subjects with impaired glucose tolerance (IGT) were randomized to control and lifestyle intervention groups. SNP rs9939609 was genotyped from 502 subjects. At baseline, those with the AA genotype had higher BMI than subjects with other genotypes (P = 0.006). The association was observed in women (P = 0.016) but not in men. During the 4‐year follow‐up, the subjects with the AA genotype had consistently the highest BMI (P = 0.009) in the entire study population. The magnitude of weight reduction was greater in the intervention group, but the risk allele did not modify weight change in either of the groups. Our results confirm the association between the common FTO variant and BMI in a cross‐sectional setting and during the long‐term lifestyle intervention. We did not observe association between FTO variant and the magnitude of weight reduction achieved by long‐term lifestyle intervention. Based on the results from the DPS, it is unlikely that the common variant of the FTO gene affects the success of lifestyle modification on weight loss.     

Meta‐analysis Added Power to Identify Variants in FTO Associated With Type 2 Diabetes and Obesity in the Asian Population

Several common variants in the intron 1 of FTO (fat mass and associated obesity) gene have been reliably associated with BMI and obesity in European populations. We analyzed two variants (rs9939609 and rs8050136) in 4,189 Chinese Han individuals and conducted a meta‐analysis of published studies in Asian population to investigate whether these variants are associated with type 2 diabetes (T2D) and obesity in Asian population. In this study, both the minor allele A of rs9939609 and the minor allele A of rs805136 were associated with increased risk of T2D, independent of measures of BMI; the odds ratios (ORs) per copy of the risk allele were 1.19 for rs9939609 (95% confidence interval (CI), 1.04–1.37; P = 0.01) and 1.22 for rs8050136 (95% CI, 1.07–1.40; P = 0.004) after adjusting for age, sex, and BMI. Our results also showed association with risk of obesity (rs9939609: OR = 1.39 (95% CI 1.04–1.85), P = 0.02; rs8050136: OR = 1.45 (95% CI 1.09–1.93), P = 0.01) but no association with overweight. These results were consistent with the pooled results from our meta‐analysis study (for diabetes, rs8050136, P = 1.3 × 10^?3; rs9939609, P = 9.8 × 10^?4; for obesity, rs8050136, P = 2.2 × 10^?7; rs9939609, P = 9.0 × 10^?9). Our findings indicate that the two variants (rs9939609 and rs8050136) in the FTO gene contribute to obesity and T2D in the Asian populations.     

The effects of FTO gene rs9939609 polymorphism on the association between breast cancer and dietary intake

Breast cancer (BC) is the leading cause of cancer‐related deaths in females worldwide and is related to genetic and environmental factors. Dietary components may strongly influence the risk of BC. A possible association was also reported between the fat mass and obesity‐associated (FTO) single‐nucleotide polymorphisms (SNPs) and BC. This study aimed to investigate the impact of FTO rs9939609 polymorphism on the association between BC and dietary intake. This study was conducted on 180 women with BC as the case group and 360 healthy women as the control group. The dietary intakes were assessed by a valid 168‐item food frequency questionnaire (FFQ). The FTO gene was genotyped for rs9939609 polymorphism. After adjusting the confounding variables, there was no significant association between dietary intake and BC in individuals without risk allele. A positive association between dietary intake of omega‐6 fatty acids and BC was found only in individuals with risk allele of FTO gene (OR: 1.31, 95% CI: 1.08–1.60, p: 0.006). FTO gene risk allele may influence the effect of diet on breast cancer risk. Further studies are needed to assess the possible effects of the FTO genotype on the association between BC risk and dietary components.     

The Effects of Genetic Variation in FTO rs9939609 on Obesity and Dietary Preferences in Chinese Han Children and Adolescents

The association of the rs9939609 single nucleotide polymorphism in FTO gene with obesity has been extensively investigated in studies of populations of European, African, and Asian ancestry. However, inconsistent results have been reported in Asian populations, and the relationship of FTO variation and dietary behaviors has only rarely been examined in Chinese children and adolescents. The aim of this study was to assess the association of rs9939609 with obesity and dietary preferences in childhood in a Chinese population. Epidemiological data including dietary preferences were collected in interviews using survey questionnaires, and rs9939609 genotype was determined by real-time PCR. The associations of rs9939609 genotypes with obesity and dietary preferences were analyzed by multivariate logistic regression using both additive and dominant models. The results showed that subjects with a TA or AA genotype had an increased risk of obesity compared with the TT participants; the odds ratios (ORs) were 1.47 (95% CI: 1.25–1.71, P = 1.73×10⁻⁶), and 3.32 (95% CI: 2.01–5.47, P = 2.68×10⁻⁶), respectively. After adjusting for age and gender, body mass index, waist circumference, hip circumference, systolic blood pressure, diastolic blood pressure, fasting blood glucose, triglycerides, and low-density lipoprotein cholesterol were higher, and high-density lipoprotein cholesterol was lower in TA and AA participants than in those with the TT genotype. After additionally controlling for body mass index, the association remained significant only for systolic blood pressure (P = 0.005). Compared with TT participants, those with the AA genotype were more likely to prefer a meat-based diet (OR = 2.81, 95% CI: 1.52–5.21). The combined OR for obesity in participants with TA/AA genotypes and preference for a meat-based diet was 4.04 (95% CI: 2.8–5.81) compared with the TT participants who preferred a plant-based diet. These findings indicate the genetic variation of rs9939609 is associated with obesity and dietary preferences in Chinese children and adolescents.     

The obesity-associated polymorphisms FTO rs9939609 and MC4R rs17782313 and endometrial cancer risk in non-Hispanic white women

Overweight and obesity are strongly associated with endometrial cancer. Several independent genome-wide association studies recently identified two common polymorphisms, FTO rs9939609 and MC4R rs17782313, that are linked to increased body weight and obesity. We examined the association of FTO rs9939609 and MC4R rs17782313 with endometrial cancer risk in a pooled analysis of nine case-control studies within the Epidemiology of Endometrial Cancer Consortium (E2C2). This analysis included 3601 non-Hispanic white women with histologically-confirmed endometrial carcinoma and 5275 frequency-matched controls. Unconditional logistic regression models were used to assess the relation of FTO rs9939609 and MC4R rs17782313 genotypes to the risk of endometrial cancer. Among control women, both the FTO rs9939609 A and MC4R rs17782313 C alleles were associated with a 16% increased risk of being overweight (p = 0.001 and p = 0.004, respectively). In case-control analyses, carriers of the FTO rs9939609 AA genotype were at increased risk of endometrial carcinoma compared to women with the TT genotype [odds ratio (OR)  = 1.17; 95% confidence interval (CI): 1.03–1.32, p = 0.01]. However, this association was no longer apparent after adjusting for body mass index (BMI), suggesting mediation of the gene-disease effect through body weight. The MC4R rs17782313 polymorphism was not related to endometrial cancer risk (per allele OR = 0.98; 95% CI: 0.91–1.06; p = 0.68). FTO rs9939609 is a susceptibility marker for white non-Hispanic women at higher risk of endometrial cancer. Although FTO rs9939609 alone might have limited clinical or public health significance for identifying women at high risk for endometrial cancer beyond that of excess body weight, further investigation of obesity-related genetic markers might help to identify the pathways that influence endometrial carcinogenesis.     

Association of the FTO rs9939609 polymorphism with obesity in Roma/Gypsy population

The rs9939609 SNP located in the first intron of the fat mass and obesity associated gene (FTO) has been found to be associated with common obesity mainly in populations of European descent. The Roma/Gypsy population as an ethnic minority of Asian Indian origin is well known for its adverse health status with a high prevalence of obesity. The main aim of this study was to examine the contribution of the rs9939609 FTO polymorphism to the high prevalence of obesity in the Roma/Gypsy population. Following a number of anthropometric measurements, the FTO rs9939609 polymorphism was genotyped in 312 Roma/Gypsy individuals. We observed significant differences in body mass index (BMI), waist circumference, and waist-to-hip ratio between different genotypes (P = 0.003, P = 0.012, and P = 0.03, respectively). The waist circumference in the subjects with AA genotype was about 7.1 cm larger than in those with TT genotypes (P = 0.005). However, the strongest association of minor allele A of the rs9939609 FTO polymorphism was found with BMI (odds ratio, 1.55; 95% confidence interval, 1.129-2.128; P = 0.007), even after adjusting for age, sex, and smoking status. This study provides the first report of allele and genotype frequencies for the rs9939609 polymorphism and also the first evidence of the association of the FTO variant with obesity in the Roma/Gypsy population.     

Association of FTO Gene Variants With Adiposity in African‐American Adolescents

The prevalence of obesity continues to increase significantly, with the largest rise in the African‐American adolescents. Genetic contributions to obesity are being identified with the advent of genome‐wide association studies (GWAS). Specifically, variants of the fat mass and obesity associated (FTO) gene have been associated with obesity in populations of European descent. The studies in African Americans have been inconclusive. To further evaluate the association of the FTO gene and adiposity in African Americans, we genotyped 47 single‐nucleotide polymorphisms (SNPs), including seven SNPs previously reported to be significant in the literature in a cohort consisting of 561 non‐Hispanic white and 497 African‐American individuals. Analysis of our data showed 17 SNPs to be associated with BMI Z‐score (BMI‐Z) in our study population. The strongest association was found in the African Americans. The most significant SNP was rs8057044, which was associated with BMI‐Z in the African Americans (P = 0.00054). SNP rs9939609 was found to be significant in the non‐Hispanic white population (P = 0.028). Our data confirm the association between FTO and adiposity suggesting that FTO is a childhood obesity susceptibility gene. Our data also identify a novel SNP of the FTO gene (rs8057044) that is associated with measures of adiposity in the African‐American population.     

Inverse Association between Obesity Predisposing FTO Genotype and Completed Suicide

The A allele of rs9939609 in the FTO gene predisposes to increased body mass index (BMI) and obesity. Recently we showed an inverse association between the obesity related A allele of rs9939609 and alcohol dependence which was replicated by others. Since this finding raises a possibility that FTO may be associated with other psychiatric phenotypes, we aimed to examine association of rs9939609 with completed suicide. We genotyped rs9939609 in 912 suicide victims and 733 controls using TaqMan approach. We observed an inverse association between suicide and the rs9939609 A allele (OR = 0.80, P = 0.002, P_cor = 0.006) with genotype distribution suggesting a co-dominant effect. Given the link between alcoholism and suicide under influence of alcohol reported in Polish population, confounding by alcohol addiction was unlikely due to apparently similar effect size among cases who were under influence of ethanol at the time of death (OR = 0.76, P = 0.003, N = 361) and those who were not (OR = 0.80, P = 0.007, N = 469). The search for genotype-phenotype correlations did not show significant results. In conclusion, our study proves that there is an inverse association between rs9939609 polymorphism in FTO gene and completed suicide which is independent from association between FTO and alcohol addiction.     

Analysis of FTO gene variants with measures of obesity and glucose homeostasis in the IRAS Family Study

Multiple studies have identified FTO gene variants associated with measures of adiposity in European-derived populations. The objective of the study was to determine whether FTO variants were associated with adiposity, including visceral and subcutaneous adipose tissue (VAT, SAT), and glucose homeostasis measures in the Insulin Resistance Atherosclerosis Family Study (IRASFS). A total of 27 SNPs in FTO intron 1, including SNPs prominent in the literature (rs9939609, rs8050136, rs1121980, rs17817449, rs1421085, and rs3751812), were genotyped in 1,424 Hispanic Americans and 604 African Americans. Multiple SNPs were associated with BMI and SAT (P values ranging from 0.001 to 0.033), and trending or associated with waist circumference (P values ranging from 0.008 to 0.099) in the Hispanic Americans. No association was observed with VAT, illustrating that FTO variants are associated with overall fat mass instead of specific fat depots. For the glucose homeostasis measures, variants were associated with fasting insulin but, consistent with other studies, after BMI adjustment, no evidence of association remained. The lack of association of FTO SNPs with insulin sensitivity is consistent with the lack of association with VAT, since these traits are strongly correlated. In the African Americans, only rs8050136 and rs9939609 were associated with BMI and WAIST (P values of 0.011 and 0.034), and associated or trending towards association with SAT (P values of 0.038 and 0.058). These results confirm that FTO variants are associated with adiposity measures, predisposing individuals to obesity by increasing overall fat mass in Hispanic Americans and to a lesser degree in African Americans.     

Association of obesity with rs1421085 and rs9939609 polymorphisms of FTO gene

The aim of this study is to investigate the genetic influence of polymorphisms in fat mass and obesity associated (FTO) gene on a sample of obese subjects and controls. Obesity is an epidemic all over the world. Several polymorphisms in the first intron of FTO gene have been associated with common forms of human obesity. In this research rs1421085 and rs9939609 polymorphisms of FTO gene were genotyped in 190 obese patients with a BMI ≥30 kg/m² (Body Mass Index) and 97 healthy controls with a BMI of 18.5–24.9. Genotyping of SNPs was performed by real-time polymerase chain reaction. Body composition was established with bioelectric impedance analysis. Waist-to-hip ratio was determined for all participants. There were no significant differences (P > 0.05) between obese cases and controls in terms of genotype frequencies of rs1421085 and rs9939609 polymorphisms in our study. Also there were no significant correlations between genotypes and obesity related (anthropometric-body composition) parameters (P > 0.05).     

Genetic variants in <Emphasis Type="Italic">FTO</Emphasis> associated with metabolic syndrome: a meta- and gene-based analysis

The objective of this study was to examine the effect of genetic variants in fat mass and obesity associated (FTO) gene on metabolic syndrome (MetS). A systematic literature search was performed and random-effects meta-analysis was used to evaluate genetic variants in FTO with MetS. A gene-based analysis was conducted to investigate the cumulative effects of genetic polymorphisms in FTO. A total of 18 studies from 13 published papers were included in our analysis. Random-effects meta-analysis yielded an estimated odds ratio of 1.19 (95% CI 1.12–1.27; P = 1.38 × 10⁻⁷) for rs9939609, 1.19 (95% CI 1.05–1.35; P = 0.008) for rs8050136, and 1.89 (95% CI 1.20–2.96; P = 0.006) for rs1421085. The gene-based analysis indicated that FTO is strongly associated with MetS (P < 10⁻⁵). This association remains after excluding rs9939609, a SNP that was frequently reported to have strong association with obesity and MetS. In this study, we concluded that the FTO gene may play a critical role in leading to MetS. Targeting this gene may provide novel therapeutic strategies for the prevention and treatment of metabolic syndrome.     

Associations of Variants in FTO and Near MC4R With Obesity Traits in South Asian Indians

Recent genome‐wide association studies show that loci in FTO and melanocortin 4 receptor (MC4R) associate with obesity‐related traits. Outside Western populations the associations between these variants have not always been consistent and in Indians it has been suggested that FTO relates to diabetes without an obvious intermediary obesity phenotype. We investigated the association between genetic variants in FTO (rs9939609) and near MC4R (rs17782313) with obesity‐ and type 2 diabetes (T2DM)‐related traits in a longitudinal birth cohort of 2,151 healthy individuals from the Vellore birth cohort in South India. The FTO locus displayed significant associations with several conventional obesity‐related anthropometric traits. The per allele increase is about 1% for BMI, waist circumference (WC), hip circumference (HC), and waist—hip ratio. Consistent associations were observed for adipose tissue‐specific measurements such as skinfold thickness reinforcing the association with obesity‐related traits. Obesity associations for the MC4R locus were weak or nonsignificant but a signal for height (P < 0.001) was observed. The effect on obesity‐related traits for FTO was seen in adulthood, but not at younger ages. The loci also showed nominal associations with increased blood glucose but these associations were lost on BMI adjustment. The effect of FTO on obesity‐related traits was driven by an urban environmental influence. We conclude that rs9939609 variant in the FTO locus is associated with measures of adiposity and metabolic consequences in South Indians with an enhanced effect associated with urban living. The detection of these associations in Indians is challenging because conventional anthropometric obesity measures work poorly in the Indian “thin‐fat” phenotype.     

Association of vitamin D receptor gene polymorphism with the risk of lung cancer: a meta-analysis

Abstract

Relationship between vitamin D receptor (VDR) gene polymorphism and the risk of lung cancer from the published reports are still conflicting. This study was conducted to evaluate the relationship between VDR TaqI (rs731236), BsmI (rs1544410) and ApaI (rs7975232) gene polymorphism and the risk of lung cancer using meta-analysis method. The association studies were identified from PubMed and Cochrane Library on 1 December 2013, and eligible investigations were included and synthesized using meta-analysis method. Six reports were recruited into this meta-analysis for the association of VDR gene polymorphism with lung cancer susceptibility. In the meta-analysis for ApaI gene polymorphism, AA genotype was associated with the risk of lung cancer in Asians. In the meta-analysis for BsmI gene polymorphism, B allele, BB genotype and bb genotype were associated with lung cancer in Asians, and B allele bb genotype were associated with lung cancer risk in overall populations; furthermore, bb genotype was associated with lung cancer risk in Caucasians. In the meta-analysis for TaqI gene polymorphism, t allele and TT genotype were associated with lung cancer in overall populations and in Caucasians. In conclusion, B allele bb genotype t allele and TT genotype were associated with lung cancer risk in overall populations. AA genotype, B allele, BB genotype and bb genotype were associated with the risk of lung cancer in Asians. Furthermore, bb genotype t allele and TT genotype was associated with lung cancer risk in Caucasians. However, more studies should be conducted to confirm it.     

BAC transgenic zebrafish reveal hypothalamic enhancer activity around obesity associated SNP rs9939609 within the human FTO gene

Single Nucleotide Polymorphisms in FTO intron 1 have been associated with obesity risk, leading to the hypothesis that FTO is the obesity‐related gene. However, other studies have shown that the FTO gene is part of the regulatory domain of the neighboring IRX3 gene and that enhancers in FTO intron 1 regulate IRX3. While Irx3 activity was shown to be necessary in the hypothalamus for the metabolic function of Irx3 in mouse, no enhancers with hypothalamic activity have been demonstrated in the risk‐associated region within FTO. In order to identify potential enhancers at the human FTO locus in vivo, we tested regulatory activity in FTO intron 1 using BAC transgenesis in zebrafish. A minimal gata2 promoter‐GFP cassette was inserted 1.3 kb upstream of the obesity associated SNP rs9939609 in a human FTO BAC plasmid. In addition to the previously identified expression domains in notochord and kidney, human FTO BAC:GFP transgenic zebrafish larvae expressed GFP in the ventral posterior tuberculum, the posterior hypothalamus and the anterior brainstem, which are also expression domains of zebrafish irx3a. In contrast, an in‐frame insertion of a GFP cassette at the FTO start codon resulted in weak ubiquitous GFP expression indicating that the promoter of FTO does likely not react to enhancers located in the obesity risk‐associated region. genesis 53:640–651, 2015. © 2015 The Authors. genesis Published by Wiley Periodicals, Inc.     

Association of vitamin D receptor BsmI (rs1544410) gene polymorphism with the chronic kidney disease susceptibility

Abstract

Association of vitamin D receptor (VDR) BsmI (rs1544410) gene polymorphism with the chronic kidney disease (CKD) susceptibility from the published reports are still conflicting. This meta-analysis was performed to evaluate the relationship between VDR BsmI (rs1544410) gene polymorphism and the risk of CKD. The association studies were identified from PubMed, Cochrane Library and China Biological Medicine Database on 1 March 2014, and eligible investigations were included and synthesized using meta-analysis method. Nine reports were recruited into this meta-analysis for the association of VDR BsmI gene polymorphism with CKD susceptibility. In this meta-analysis for overall populations, the BsmI B allele BB genotype and bb genotype were not associated with the risk of CKD (B allele: OR?=?1.12, 95% CI: 0.88–1.44, p?=?0.36; BB genotype: OR?=?1.15, 95% CI: 0.81–1.62, p?=?0.43; bb genotype: OR?=?0.86, 95% CI: 0.61–1.20, p?=?0.36). Furthermore, VDR BsmI gene polymorphism was not associated with CKD susceptibility in Asians and in Caucasians. In conclusion, the BsmI gene polymorphism was not associated with CKD susceptibility in overall populations, in Asians and in Caucasians. However, more studies should be conducted to confirm it.