Dietary polyunsaturated fatty acids and the Pro12Ala polymorphisms of PPARG regulate serum lipids through divergent pathways: a randomized crossover clinical trial

Pihlajamäki, Jussi; Schwab, Ursula; Kaminska, Dorota; Ågren, Jyrki; Kolehmainen, Marjukka; Paananen, Jussi; Laakso, Markku; Uusitupa, Matti

doi:10.1007/s12263-015-0493-z

Cited by 14 publications

(18 citation statements)

References 35 publications

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“… 32 Since PPARgamma-2 is an important regulator of lipid homeostasis and inflammation, it is therefore suspected to affect the development of CTD and related cardiovascular disorders. 6 – 8 However, the exact role of PPARgamma-2 and ADRB3 genes in CTD and the prevalence of selected polymorphisms is not well known. Thus, in this study, we intended to elucidate its genetic role in lipid disorders, which affects the cardiovascular risk during CTD.…”

Section: Discussionmentioning

confidence: 99%

“… 4 , 5 For example, the common Pro12Ala polymorphism of PPARgamma-2 is associated with dyslipidemia and many studies suggest its functional and prognostic consequences in cardiometabolic diseases (mainly the protective effect of the Ala12 allele on diabetes and myocardial infarction). 6 , 7 Moreover, activation of the PPARgamma-2 gene changes inflammatory processes and is suspected to participate in the development of CTD, eg, rheumatoid arthritis. 7 , 8 But some studies do not confirm the association of the Pro12Ala polymorphism with rheumatoid arthritis.…”

Section: Introductionmentioning

confidence: 99%

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PPARgamma-2 and ADRB3 polymorphisms in connective tissue diseases and lipid disorders

Grygiel-Górniak

Ziółkowska-Suchanek

Kaczmarek

et al. 2018

CIA

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BackgroundThe aim of the research genetic study was to investigate the association between variants (C1431T and Pro12Ala) of the peroxisome proliferator-activated receptor (PPARgamma-2) gene, Trp64Arg polymorphism of the beta-3-adrenergic receptor gene and lipid profile in Polish population including group of 103 patients with connective tissue disease (CTD) and 103 sex-and age-matched controls in context of statin use.MethodsAnthropometric and biochemical parameters were measured by routine methods, followed by genotyping (TagMan® Genotyping Assays, PCR-restriction fragment length polymorphism analysis). Nearly 30% of CTD patients used statins and 10% of the control group.ResultsAlthough there were no differences between alleles and genotypes prevalence between CTD vs control groups, interesting lipid-gene associations were noted in this study. A higher level of triglycerides (TAG) and TAG/high-density lipoprotein (HDL) ratios was observed in CTD patients compared to controls. Similar differences were noted in CTD and control groups without statin treatment. Atherogenic markers: the atherogenic index of plasma, TAG/HDL and low-density lipoprotein/HDL ratio were low in the analyzed groups. Of the six analyzed polymorphisms, the Pro12Pro or C14131C or Trp64Trp genotypes were related to higher TAG and TAG/HDL ratios in patients with CTD; however, the highest TAG values were observed in the presence of the Trp64Trp genotype.ConclusionLipid disorders were present in both groups independent of statin treatment (mixed dyslipidemia and hypercholesterolemia were observed in the CTD and control groups, respectively). The risk of dyslipidemia increases with age. The presence of Pro12Pro, C14131C and Trp64Trp genotypes is related to higher TAG level in CTDs, and of these the Trp64Trp variant most reliably predicts hypertriglyceridemia.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

PPARgamma-2 and ADRB3 polymorphisms in connective tissue diseases and lipid disorders

Grygiel-Górniak

Ziółkowska-Suchanek

Kaczmarek

et al. 2018

CIA

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“…Another study by Pihlajamäki et al. ( 13 ) investigating the relation between the PPARG Pro12Ala and polyunsaturated fatty acids (PUFA) and its influence on serum lipid profile also employed the GBR approach. They were unable to find any effect of PUFA on the PPARG gene, which also remained unaffected by the diet–genotype interaction.…”

Section: Discussionmentioning

confidence: 99%

Genotype-based recall to study metabolic effects of genetic variation: a pilot study ofPPARGPro12Ala carriers

Kamble

Gustafsson

Pereira

et al. 2017

Upsala Journal of Medical Sciences

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AimTo assess practical implications of genotype-based recall (GBR) studies, an increasingly popular approach for in-depth characterization of genotype–phenotype relationships.MethodsWe genotyped 2500 participants from the Swedish EpiHealth cohort and considered loss-of-function and missense variants in genes with relation to cardiometabolic traits as the basis for our GBR study. Therefore, we focused on carriers and non-carriers of the PPARG Pro12Ala (rs1801282) variant, as it is a relatively common variant with a minor allele frequency (MAF) of 0.14. It has also been shown to affect ligand binding and transcription, and carriage of the minor allele (Ala12) is associated with a reduced risk of type 2 diabetes. We re-invited 39 Pro12Pro, 34 Pro12Ala, and 30 Ala12Ala carriers and performed detailed anthropometric and serological assessments.ResultsThe participation rates in the GBR study were 31%, 44%, and 40%, and accordingly we included 12, 15, and 13 individuals with Pro12Pro, Pro12Ala, and Ala12Ala variants, respectively. There were no differences in anthropometric or metabolic variables among the different genotype groups.ConclusionsOur report highlights that from a practical perspective, GBR can be used to study genotype–phenotype relationships. This approach can prove to be a valuable tool for follow-up findings from large-scale genetic discovery studies by undertaking detailed phenotyping procedures that might not be feasible in large studies. However, our study also illustrates the need for a larger pool of genotyped or sequenced individuals to allow for selection of rare variants with larger effects that can be examined in a GBR study of the present size.

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“…С формированием ожирения у детей могут быть связаны полиморфизмы P12A (rs18012820) гена PPARG, C112A (rs429358) и A158C (rs7412) гена аполипопротеина E (APOЕ), ответственные за развитие ожирения у взрослых [19,20]. Вместе с полиморфизмом G75A (rs670) гена аполипопротеина A1 (APOА1) перечисленные однонуклеотидные полиморфизмы являются причиной гетерогенных изменений липидного спектра при одинаковых диетологических вмешательствах у разных людей [21][22][23], что указывает на перспективность их изучения, особенно в нутригенетическом аспекте.…”

Section: обоснованиеunclassified

Polymorphism of PPARG (P12A), APOA1 (G75A), and APOE (C112A and A158C) Genes in Children with Obesity and Arterial Hypertension: A Case-Control Study

Ковтун

Устюжанина

2018

Vopr. sovr. pediatr.

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Background. The genetic nature of a comorbid development of obesity and arterial hypertension (AH) in children is poorly studied. In this regard, it is important to study genes, the polymorphism of which is associated with disturbances in both metabolic processes and control of arterial pressure. Objective. Our aim was to study the association of polymorphisms P12A (rs1801282) of the PPARG gene, G75A (rs670) of the apolipoprotein A1 gene (APOA1), C112A (rs429358) and A158C (rs7412) of the apolipoprotein E gene (APOE) with the development of obesity and AH in children. Methods. The study included children with obesity and AH (case) and healthy children (control) aged from 10 to 17 years. Gene polymorphism was studied by polymerase chain reaction in real time. We determined blood concentrations of cholesterol and its fractions, triglycerides, apoA1, apoB, fasting glucose and glucose tolerance test for all children. Results. Groups of patients with obesity and AH (n = 69) and healthy children (n = 49) were comparable by age and sex. In the case group, there were more carriers of the A allele (25 versus 9% in the healthy group; p = 0.002) and the AA genotype (13% and 2%, respectively; df = 2, p = 0.031) of APOE C112A polymorphism. PPARG and APOA1 polymorphisms as well as APOE A158C polymorphism were not associated with the development of obesity and AH in children. The carriers of the APOE e2 allele had lower concentrations of low density lipoproteins and apoB in the blood; the carriers of the PPARG G allele had lower glycemia values, and the carriers of the A allele of APOA1 G75A polymorphism had higher glycemia values. Conclusion. The APOE C112A polymorphism is associated with a comorbid development of obesity and AH in children. The pathogenetic significance of PPARG and APOA1 polymorphisms warrants further investigation.

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Dietary polyunsaturated fatty acids and the Pro12Ala polymorphisms of PPARG regulate serum lipids through divergent pathways: a randomized crossover clinical trial

Cited by 14 publications

References 35 publications

<em>PPARgamma-2</em> and <em>ADRB3 </em>polymorphisms in connective tissue diseases and lipid disorders

<em>PPARgamma-2</em> and <em>ADRB3 </em>polymorphisms in connective tissue diseases and lipid disorders

Genotype-based recall to study metabolic effects of genetic variation: a pilot study ofPPARGPro12Ala carriers

Polymorphism of PPARG (P12A), APOA1 (G75A), and APOE (C112A and A158C) Genes in Children with Obesity and Arterial Hypertension: A Case-Control Study

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