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Effects of FTO RS9939906 and MC4R RS17782313 on obesity, type 2 diabetes mellitus and blood pressure in patients with hypertension.

ABSTRACT: Genetic variants of the FTO gene rs9939609 A/T and the MC4R gene rs17782313 C/T have been associated with obesity. Individuals with mutations in MC4R gene have lower blood pressure (BP), independently of obesity. This study aimed to investigate the association of FTO rs9939609 and MC4R rs17782313 with anthropometric indexes, BP, and type 2 diabetes mellitus among hypertensive patients.We genotyped 217 individuals (86 men and 131 women) with hypertension (systolic or diastolic BP???140/90 mmHg or using antihypertensive drugs). Diabetes mellitus was diagnosed according to the American Diabetes Association criteria. Waist and neck circumferences (cm), Body Adiposity Index (BAI,%), Lipid Accumulation Product Index (LAP, cm.mmol.l) and body mass index (BMI, kg/m²) were analyzed using analysis of covariance or modified Poisson's regression.Rare allele frequencies were 0.40 for A for FTO rs9939609 and 0.18 for C for MC4R rs17782313. A positive association of FTO rs9939609 and MC4R rs17782313 with BMI was observed in the overall sample. Among men and women, neck circumference was associated with the FTO genotype and, for women, MC4R genotype. In contrast, in men we found a negative association of MC4R rs17782313 with diastolic BP (TT 90.1 ±12.2, TC/CC 83.2 ±12.1; P?=?0.03) and borderline association for systolic BP after controlling for age and BMI.Common genetic variants of FTO rs9939609 have positive associations with BMI and neck circumference and MC4R rs17782313 in women, but a negative association with diastolic and mean blood pressure in men with hypertension.

SUBMITTER: Marcadenti A

PROVIDER: S-EPMC3711897 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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Effects of FTO RS9939906 and MC4R RS17782313 on obesity, type 2 diabetes mellitus and blood pressure in patients with hypertension.

Marcadenti Aline A Fuchs Flavio D FD Matte Ursula U Sperb Fernanda F Moreira Leila B LB Fuchs Sandra C SC

Cardiovascular diabetology 20130712

<h4>Background</h4>Genetic variants of the FTO gene rs9939609 A/T and the MC4R gene rs17782313 C/T have been associated with obesity. Individuals with mutations in MC4R gene have lower blood pressure (BP), independently of obesity. This study aimed to investigate the association of FTO rs9939609 and MC4R rs17782313 with anthropometric indexes, BP, and type 2 diabetes mellitus among hypertensive patients.<h4>Methods</h4>We genotyped 217 individuals (86 men and 131 women) with hypertension (systol ...[more]

PMID: 23849767

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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:BackgroundThere is no evidence from randomized trials to support a strategy of lowering systolic blood pressure below 135 to 140 mm Hg in persons with type 2 diabetes mellitus. We investigated whether therapy targeting normal systolic pressure (i.e., <120 mm Hg) reduces major cardiovascular events in participants with type 2 diabetes at high risk for cardiovascular events.MethodsA total of 4733 participants with type 2 diabetes were randomly assigned to intensive therapy, targeting a systolic pressure of less than 120 mm Hg, or standard therapy, targeting a systolic pressure of less than 140 mm Hg. The primary composite outcome was nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes. The mean follow-up was 4.7 years.ResultsAfter 1 year, the mean systolic blood pressure was 119.3 mm Hg in the intensive-therapy group and 133.5 mm Hg in the standard-therapy group. The annual rate of the primary outcome was 1.87% in the intensive-therapy group and 2.09% in the standard-therapy group (hazard ratio with intensive therapy, 0.88; 95% confidence interval [CI], 0.73 to 1.06; P=0.20). The annual rates of death from any cause were 1.28% and 1.19% in the two groups, respectively (hazard ratio, 1.07; 95% CI, 0.85 to 1.35; P=0.55). The annual rates of stroke, a prespecified secondary outcome, were 0.32% and 0.53% in the two groups, respectively (hazard ratio, 0.59; 95% CI, 0.39 to 0.89; P=0.01). Serious adverse events attributed to antihypertensive treatment occurred in 77 of the 2362 participants in the intensive-therapy group (3.3%) and 30 of the 2371 participants in the standard-therapy group (1.3%) (P<0.001).ConclusionsIn patients with type 2 diabetes at high risk for cardiovascular events, targeting a systolic blood pressure of less than 120 mm Hg, as compared with less than 140 mm Hg, did not reduce the rate of a composite outcome of fatal and nonfatal major cardiovascular events. (ClinicalTrials.gov number, NCT00000620.)

Dataset Information

Effects of FTO RS9939906 and MC4R RS17782313 on obesity, type 2 diabetes mellitus and blood pressure in patients with hypertension.

Publications

Effects of FTO RS9939906 and MC4R RS17782313 on obesity, type 2 diabetes mellitus and blood pressure in patients with hypertension.

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