Dataset Information

Relationships between FTO rs9939609, MC4R rs17782313, and PPAR? rs1801282 polymorphisms and the occurrence of selected metabolic and hormonal disorders in middle-aged and elderly men - a preliminary study.

ABSTRACT: Metabolic disorders, including MetS, obesity, and lipid disorders, may be related to genetic factors. Metabolic disorders are associated with decreased TS levels in aging men. The aim of this study was to evaluate the relationship between FTO rs9939609, MC4R rs17782313, and PPAR? rs1801282 polymorphisms and the presence of MetS and its components, the concurrent lipid disorders, as well as sex hormone concentrations.This study involved 272 men of Caucasian descent aged 50-75 years. Lipid profile, including TCh, LDL, HDL, and TG, was evaluated by spectrophotometric method. Anthropometric measurements concerned WC and blood pressure. MetS was diagnosed according to the criteria of the IDF. Sex hormone profile, including TST, FTS, E2, DHEAS, and SHBG, was examined using enzyme-linked immunosorbent assay. Polymorphisms within FTO, MC4R, and PPAR? genes were identified using polymerase chain reaction-restriction fragments length polymorphism.This study did not show links between the analyzed genetic polymorphisms and the presence of MetS, T2DM, HT, and obesity. However, higher concentrations of TCh and LDL were found in men with the FTO rs9939609 polymorphism in the recessive mode of inheritance (P=0.03 and P=0.05, respectively). Lower WC was found to be associated with MC4R rs17782313 gene inherited in the same model (P=0.005).FTO rs9939609, MC4R rs17782313, and PPAR? rs1801282 polymorphisms seem to have little effect on the incidence of metabolic malfunctions and no effect on androgen-related disorders in the examined middle-aged and elderly men.

SUBMITTER: Rotter I

PROVIDER: S-EPMC5126003 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Publications

Relationships between <i>FTO</i> rs9939609, <i>MC4R</i> rs17782313, and <i>PPARγ</i> rs1801282 polymorphisms and the occurrence of selected metabolic and hormonal disorders in middle-aged and elderly men - a preliminary study.

Rotter Iwona I Skonieczna-Żydecka Karolina K Kosik-Bogacka Danuta D Adler Grażyna G Rył Aleksandra A Laszczyńska Maria M

Clinical interventions in aging 20161123

<h4>Purpose</h4>Metabolic disorders, including MetS, obesity, and lipid disorders, may be related to genetic factors. Metabolic disorders are associated with decreased TS levels in aging men. The aim of this study was to evaluate the relationship between <i>FTO</i> rs9939609, <i>MC4R</i> rs17782313, and <i>PPARγ</i> rs1801282 polymorphisms and the presence of MetS and its components, the concurrent lipid disorders, as well as sex hormone concentrations.<h4>Subjects and methods</h4>This study inv ...[more]

PMID: 27920511

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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: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.

Dataset Information

Relationships between FTO rs9939609, MC4R rs17782313, and PPAR? rs1801282 polymorphisms and the occurrence of selected metabolic and hormonal disorders in middle-aged and elderly men - a preliminary study.

Publications

Relationships between <i>FTO</i> rs9939609, <i>MC4R</i> rs17782313, and <i>PPARγ</i> rs1801282 polymorphisms and the occurrence of selected metabolic and hormonal disorders in middle-aged and elderly men - a preliminary study.

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