Dataset Information

Combined effects of FTO rs9939609 and MC4R rs17782313 on elevated nocturnal blood pressure in the Chinese Han population.

ABSTRACT: In this study we investigated the association of FTO rs9939609 and MC4R rs17782313 with elevated blood pressure in the Chinese Han population, and analysed the relationship between the rs9939609 and rs17782313 variants.We tested the rs9939609 and rs17782313 variants with the sequence-retrieval method.The increase in odds ratios of the A allele of rs9939609 and the C allele of rs17782313 for nocturnal blood pressure were 1.37 and 1.69. The nocturnal blood pressure of participants simultaneously carrying the A and C alleles was significantly higher than the blood pressure of those carrying neither FTO nor MC4R risk alleles (p < 0.05), and that of the controls carrying only the A or C alleles (p < 0.05). No association between the FTO or MC4R genes with daytime hypertension was found in this Chinese population (p > 0.05).Our data suggest that the rs9939609 and rs17782313 variants may be significantly associated with nocturnal but not daytime blood pressure levels and their combined effects were significant in this Chinese Han population.

SUBMITTER: Sun Y

PROVIDER: S-EPMC4816968 | biostudies-literature | 2016 Jan-Feb

REPOSITORIES: biostudies-literature

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Combined effects of FTO rs9939609 and MC4R rs17782313 on elevated nocturnal blood pressure in the Chinese Han population.

Sun Yanlei Y Sun Jiazhong J Wu Jun J Yang Mei M

Cardiovascular journal of Africa 20150831 1

<h4>Aim</h4>In this study we investigated the association of FTO rs9939609 and MC4R rs17782313 with elevated blood pressure in the Chinese Han population, and analysed the relationship between the rs9939609 and rs17782313 variants.<h4>Methods</h4>We tested the rs9939609 and rs17782313 variants with the sequence-retrieval method.<h4>Results</h4>The increase in odds ratios of the A allele of rs9939609 and the C allele of rs17782313 for nocturnal blood pressure were 1.37 and 1.69. The nocturnal blo ...[more]

PMID: 26324055

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Project description:Although the fat mass and obesity (FTO) and melanocortin-4 receptor (MC4R) genes have been consistently associated with obesity risk, the association between the obesity-risk alleles with type 2 diabetes is still controversial. In some recent meta-analyses in which significant results have been reported, the associations disappeared after adjustment for body mass index (BMI). However gene-diet interactions with dietary patterns have not been investigated. Our main aim was to analyze whether these associations are modulated by the level of adherence to the Mediterranean Diet (MedDiet).Case-control study in 7,052 high cardiovascular risk subjects (3,430 type 2 diabetes cases and 3,622 non-diabetic subjects) with no differences in BMI. Diet was assessed by validated questionnaires. FTO-rs9939609 and MC4R-rs17782313 were determined. An aggregate genetic score was calculated to test additive effects. Gene-diet interactions were analyzed.Neither of the polymorphisms was associated with type 2 diabetes in the whole population. However, we found consistent gene-diet interactions with adherence to the MedDiet both for the FTO-rs9939609 (P-interaction=0.039), the MC4R-rs17782313 (P-interaction=0.009) and for their aggregate score (P-interaction=0.006). When adherence to the MedDiet was low, carriers of the variant alleles had higher type 2 diabetes risk (OR=1.21, 95%CI: 1.03-1.40; P=0.019 for FTO-rs9939609 and OR=1.17, 95%CI:1.01-1.36; P=0.035 for MC4R-rs17782313) than wild-type subjects. However, when adherence to the MedDiet was high, these associations disappeared (OR=0.97, 95%CI: 0.85-1.16; P=0.673 for FTO-rs9939609 and OR=0.89, 95%CI:0.78-1.02; P=0.097 for MC4R-rs17782313). These gene-diet interactions remained significant even after adjustment for BMI. As MedDiet is rich in folate, we also specifically examined folate intake and detected statistically significant interaction effects on fasting plasma glucose concentrations in non-diabetic subjects. However these findings should be interpreted with caution because folate intake may simply reflect a healthy dietary pattern.These novel results suggest that the association of the FTO-rs9939609 and the MC4R-rs17782313 polymorphisms with type 2 diabetes depends on diet and that a high adherence to the MedDiet counteracts the genetic predisposition.

Project description: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.

Project description:MC4R represents a key player involved in melanocortin-mediated control of energy balance. Recently identified near MC4R variant rs17782313 (T > C) can serve as a contributing factor for obese phenotype but its association with obesity has never been sought in a sample of the Pakistani population. The role of genetic variants as causal factors varies across populations. Association studies in a specific population can help us to distinguish global from local gene-gene and gene-environment interactions. This is the first study that investigated the association of rs17782313 with obesity and various obesity-linked anthropometric, metabolic, physical, and behavioural traits in Pakistani subjects including 306 OW/OB (overweight and obese) and 300 NW (normal weight) individuals. The comparison of various aforementioned obesity-linked continuous and categorical variables between OW/OB and NW subjects revealed that almost all variables were found significantly aberrant (p < 0.05) in OW/OB subjects as compared to their age- and gender-matched NW controls indicating greater risk of developing various cardio-metabolic disorders. The genotyping of rs17782313 showed significant association of this variant with obesity and obesity-linked anthropometric traits in females suggesting the gender-specific effect of this variant in our population. The minor allele C increased the risk of obesity by 1.55 times (95% CI = 1.1-2.18, p = 0.01) whereas homozygous CC genotype increased the risk by 2.43 times (95% CI = 1.19-4.96, p = 0.015) in females. However, no association of rs17782313 was observed with any of the obesity-linked metabolic, physical, and behavioural traits except random eating timings. In conclusion, the current study significantly contributes to the knowledge of the genetic proneness to obesity in Pakistani females. This could also be helpful for forthcoming meta-analysis studies elucidating which variants are truly associated with the susceptibility to develop an obese phenotype.

Project description:BackgroundFat-mass and obesity-associated (FTO) gene is a gene located in chromosome region 16q12.2. Genetic variants in FTO are associated with the obesity phenotype in European and Hispanic populations. However, this association still remains controversial in Asian population. We aimed to test the association of FTO genetic variants with obesity and obesity-related metabolic traits among children living in Beijing, China.MethodsWe genotyped FTO variants rs9939609 in 670 children (332 girls and 338 boys) aged 8-11 years living in Beijing, and analyzed its association with obesity and obesity-related metabolic traits. Overweight and obesity were defined by age- and sex-specific BMI reference for Chinese children. Obesity-related metabolic traits included fasting plasma glucose, lipid profiles, leptin, ghrelin, adiponectin and blood pressures.ResultsThe frequency of rs9939609 A allele was 12.2%, which was 21.9% for the heterozygote and 1.2% for the homozygote of the A allele. The obesity prevalence among the carriers of AA/AT genotypes was significantly higher than that among those with TT genotype (36.4% vs. 22.6%, P=0.004). Compared to the carrier of TT genotype, the likelihood of obesity was 1.79 (95% confidence interval (95% CI) 1.20-2.67, P=0.004) for the carrier of AA/AT genotype, after adjustment of sex, age and puberty stages. The BMI Z-score of children with AA/AT genotype were significantly higher than that of their counterparts with the TT genotype (1.1±0.1 vs. 0.8±0.1, P=0.02). The concentration of triglyceride was 1.03±0.52 mmol/L among TT carrier and 1.13±0.68 mmol/L among AA/AT carrier (P=0.045). While, the concentrations of adiponectin were 18.0±0.4 μg/ml among carriers of TT and 16.2±0.7 μg/ml among subjects with AA/AT genotype (P=0.03). The level of glucose marginally increased in the AA/AT genotype subjects (4.67±0.40 mmol/L vs. 4.60±0.35 mmol/L, P=0.08). The evidence of association was reduced after adjustment for BMI (P=0.38 for triglyceride, P=0.20 for adiponectin and glucose). There was weak evidence of association between rs9939609 and other obesity-related metabolic traits including total cholesterol (3.92±0.03 mmol/L vs. 4.02±0.05 mmol/L, P=0.10), insulin (2.69±1.77 ng/ml vs. 3.12±2.91 ng/ml, P=0.14), and insulin resistance (HOMA-IR 0.56±0.03 vs. 0.66±0.05, P=0.10).ConclusionsGenetic variation in the FTO gene associates with obesity in Chinese children.

Dataset Information

Combined effects of FTO rs9939609 and MC4R rs17782313 on elevated nocturnal blood pressure in the Chinese Han population.

Publications

Combined effects of FTO rs9939609 and MC4R rs17782313 on elevated nocturnal blood pressure in the Chinese Han population.

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