Original Research PaperThe interaction of FTO-rs9939609 polymorphism with artichoke leaf extract effects on cardiometabolic risk factors in hypertriglyceridemia: A randomized clinical trial
Introduction
Elevated serum levels of triglyceride have independently been associated with increased risk of cardiovascular disease [1]. Hypertriglyceridemia commonly coexist with multiple risk factors including prothrombotic and proinflammatory biomarkers, increased plasma glucose levels, hypertension, obesity and metabolic syndrome [2]. Furthermore, patients with very high serum levels of triglyceride (more than 10 mmol/L) are at risk for acute pancreatitis [3].
The fat mass and obesity associated (FTO) gene encodes an enzyme which is present in many tissues, especially in the hypothalamus, the center of energy homeostasis [4]. The rs9939609 polymorphism in FTO gene is a potential candidate genetic variant for obesity and metabolic syndrome [[5], [6], [7]]. Since hypertriglyceridemia is a common feature of obesity and metabolic syndrome [8], the FTO variant rs9939609 may be implicated in the susceptibility to hypertriglyceridemia. Furthermore, A allele of rs9939609 variant gene of FTO, the risk allele of adiposity, is associated with higher triglyceride, insulin and glucose levels, and that these associations are dependent on body mass index (BMI) [7]. Differences in individuals' genetic background may modulate the effect of the intervention on outcome variables [6,[9], [10], [11], [12], [13], [14]].
Artichoke (Cynara scolymus L., Asteraceae family) is used both as a healthy food and as a medicinal herb worldwide [15]. Traditionally, artichoke leaf extract (ALE) was used to treat dyspepsia and hepato-biliary diseases. Scientific researches indicated antioxidant [[16], [17], [18]], hepatoprotective [16,17], anti-atherosclerotic [19,20] and glucose and lipid lowering effects [[21], [22], [23], [24]] for ALE. The safety of ALE supplementation has been demonstrated in animal and human studies. There were no reported mutagenic and genotoxic effects in mice at <2000 mg/kg [25]. Furthermore, only mild and transient adverse events relating to the gastro-intestinal system have been reported in some clinical trials following ALE consumption [[22], [23], [24], [25], [26]].
Recently, some clinical trials have shown the efficacy of ALE in improvement of triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) concentration [14,21,22,24,27,28], whereas others failed to show any improvement [26]. Besides, rs9939609 variant in FTO have shown an association with higher triglyceride level [7]. To best our knowledge, there is limited evidence for effects of ALE supplementation on cardiometabolic parameters in hypertriglyceridemi patients. Thus, the present study was aimed to investigate the effects of artichoke leaf extract on cardiometabolic risk factors in hypertriglyceridemic patients and an interaction with rs9939609 variant in FTO gene.
Section snippets
Study design and participants
The present randomized, double-blind, placebo-controlled clinical trial was a part of a case-control study on metabolic syndrome gene polymorphism with 185 sample size. The intervention part was carried out on hypertriglicerdemic patients. The sample size was calculated based on the changes in serum fasting blood sugar (FBS) level reported by Rondanelli et al. [24]. Considering a confidence level of 95% and power of 80% and anticipating a possible dropout rate of 10%, 26 patients with
Results
Of the 185 subjects who were screened for FTO-rs9939609 polymorphism, 25.9% (n = 48) were homozygous for T allele, 65.4% (n = 121) were heterozygote, and 8.6% (n = 16) were homozygous for C allele (data not shown). During the 12-week follow-up, four patients were withdrawn from the study (2 patients from each intervention and placebo group) as shown in Fig. 1. None of the dropouts were related to the adverse effects of ALE or placebo. Moreover, there were no reports of adverse effects in
Discussion
The present study was found that ALE supplementation did not change the anthropometric and biochemical variables in patients with hypertriglyceridemia over 12 weeks. However, the significant interaction between ALE supplementation and FTO-rs9939609 polymorphism was found on TC, LDL-C and TG level. Moreover, TG level significantly affected by FTO-rs9939609 polymorphism regardless of intervention.
The FTO gene, located on chromosome 16q12.2, encodes a nuclear protein of non-haem Fe(II) and
Conclusion
Our finding showed that ALE supplementation did not affect anthropometric and biochemical indices in Iranian hypertriglyceridemic patients. Moreover, this study suggested the interaction between the response of lipid profile to ALE supplementation and FTO-rs9939609 polymorphism.
Accordingly, polymorphism genotyping helps the clinicians in choosing the appropriate treatment for patients with hypertriglyceridemia. Moreover, individuals carrying A allele of FTO-rs9939609 polymorphism may benefit
Conflict of interest
The authors declare that they have no conflicts of interest.
Acknowledgements
We are grateful to the subjects for their participation in this study. The authors also would like to acknowledge Dineh Iran. Co. for preparing of Artichoke Leaf Extract and placebo tablets. This study was supported by a Grant from the Research Vice Chancellor, Tabriz University of Medical Sciences, Tabriz, Iran (grant number: 5/97/4653). The results of this article are derived from the Ph.D. thesis of Khatereh Rezazadeh (NO, D/41).
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