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Vitamin D Receptor Gene Polymorphisms and the Risk of Metabolic Syndrome (MetS): A Meta-Analysis.
Totonchi, H, Rezaei, R, Noori, S, Azarpira, N, Mokarram, P, Imani, D
Endocrine, metabolic & immune disorders drug targets. 2021;(5):943-955
Abstract
BACKGROUND Several studies have assessed the association between the vitamin D receptor (VDR) polymorphism and the risk of metabolic syndrome (MetS). However, the results were inconsistent and inconclusive. Therefore, we conducted a meta-analysis to clarify the exact association between the vitamin D receptor (VDR) polymorphisms and the risk of MetS. METHODS All accessible studies reporting the association between the FokI (rs2228570) or/and TaqI (rs731236) or/and BsmI (rs1544410) or/and ApaI (rs7975232 polymorphisms of the Vitamin D Receptor and susceptibility to MetS published prior to February 2019 were systematically searched in Web of Science, Scopus, and PubMed. After that, Odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were estimated to evaluate the strength of the association in five genetic models. RESULTS A total of 9 articles based on four gene variations, and comprising 3348 participants with 1779 metabolic syndrome patients were included. The overall results suggested a significant association between BsmI (rs1544410) polymorphism and MetS susceptibility in recessive model (OR, 0.72, 95% CI, 0.55-0.95, fixed effect model), allelic model (OR, 0.83, 95% CI, 0.72-0.95, fixed effect model), and bb vs BB (OR, 0.65, 95% CI, 0.46-0.93, fixed effect). However, no significant association was identified between TaqI (rs731236) polymorphism, ApaI (rs7975232) polymorphism, and FokI (rs2228570) polymorphism and MetS. CONCLUSION This meta-analysis suggested an association between the BsmI (rs1544410) polymorphism and MetS. Indeed, BsmI (rs1544410) acts as a protective factor in the MetS. As a result, the VDR gene could be regarded as a promising pharmacological and physiological target in the prevention or treatment of the MetS.
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Genetics of gallstone disease.
Rebholz, C, Krawczyk, M, Lammert, F
European journal of clinical investigation. 2018;(7):e12935
Abstract
BACKGROUND Gallstone disease (GD) belongs to the most frequent disorders in gastroenterology and causes high costs in our health-care systems. Gallstones are uncommon in children but frequent in adults, in particular in women, and are triggered by exogenous risk factors. Here, we summarize the current knowledge concerning the contribution of inherited predisposition to gallstone risk. DESIGN In this review, we present the current data and recent research on the genetics of gallstone disease. RESULTS Several GD-predisposing gene variants have been reported, with most prominent effects being conferred by a common variant (p.D19H) of the hepatic and intestinal cholesterol transporter ABCG5/G8. A smaller group of patients might develop gallstones primarily due low phosphatidylcholine concentrations in bile as a result of loss-of-function mutations of the ABCB4 transporter (low phospholipid-associated cholelithiasis syndrome). Regardless of the origin, the risk factors for gallstones lead to the supersaturation of bile with insoluble compounds, in particular cholesterol. As result, cholesterol stones develop and present the most frequent type of gallstones. Laparoscopic cholecystectomy with low morbidity and mortality is currently the most common and effective method for the therapy of symptomatic gallbladder stones. CONCLUSIONS Gallstone disease represents a multifactorial condition and previous studies have identified the major genetic contributors to gallstone formation. The increasing knowledge about the pathomechanisms of hepatobiliary metabolism and GD as well as the identification of additional risk factors might help to overcome the current invasive therapy by specific lifestyle intervention and precise molecular treatment.
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Inherited and acquired disorders of magnesium homeostasis.
Wolf, MT
Current opinion in pediatrics. 2017;(2):187-198
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Abstract
PURPOSE OF REVIEW Magnesium (Mg) imbalances are frequently overlooked. Hypermagnesemia usually occurs in preeclamptic women after Mg therapy or in end-stage renal disease patients, whereas hypomagnesemia is more common with a prevalence of up to 15% in the general population. Increasing evidence points toward a role for mild-to-moderate chronic hypomagnesemia in the pathogenesis of hypertension, type 2 diabetes mellitus, and metabolic syndrome. RECENT FINDINGS The kidneys are the major regulator of total body Mg homeostasis. Over the last decade, the identification of the responsible genes in rare genetic disorders has enhanced our understanding of how the kidney handles Mg. The different genetic disorders and medications contributing to abnormal Mg homeostasis are reviewed. SUMMARY As dysfunctional Mg homeostasis contributes to the development of many common human disorders, serum Mg deserves closer monitoring. Hypomagnesemic patients may be asymptomatic or may have mild symptoms. In severe hypomagnesemia, patients may present with neurological symptoms such as seizures, spasms, or cramps. Renal symptoms include nephrocalcinosis and impaired renal function. Most conditions affect tubular Mg reabsorption by disturbing the lumen-positive potential in the thick ascending limb or the negative membrane potential in the distal convoluted tubule.
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Haplotyping strategy highlights the specificity of FTO gene association with polycystic ovary syndrome in Tunisian women population.
Ben Salem, A, Attaoua, R, Mtiraoui, N, Meddeb, S, Kacem, O, Ajina, M, Souissi, M, Poucheret, P, Normand, C, Mahjoub, T, et al
Gene. 2015;(2):166-70
Abstract
The FTO (fat mass and obesity associated) gene was associated with different metabolic disorders in populations from different origins but with great difference between African and non-African populations. North-African populations combine many genetic backgrounds, among which African, Berber and Caucasian components, which makes North-Africans a good model for studying the genetic association of FTO. In the present investigation we explored the association of FTO gene with polycystic ovary syndrome (PCOS) in a population from Tunisia (n=278). Single nucleotide polymorphisms (SNPs) used in this study were previously associated in non-African populations: rs8050136 (A/C), rs9939609 (A/T), rs9930506 (G/A), or in both African and non-African populations: rs8057044 (A/G). Genotyping was performed by allelic discrimination method on StepOne real-time PCR system or KASPar technology. Linkage disequilibrium (LD) pattern was assessed by HAPLOVIEW and reconstruction of haplotypes was performed by PHASE, while statistical analyses were performed using StatView and GoldenHelix programs. Among the 13 haplotypes in the population, three (h1, h7 and h13) were strongly associated with PCOS notably h13 (P<0.0001, OR95%CI=0.040 [0.005-0.294]) while SNPs display weaker association. Moreover the LD pattern in FTO in the Tunisian population (r(2) index) was intermediary between those of Caucasian and Africans. This highlights the need for studying the genetics of complex disorders in the North-African populations taking into-account the haplotype structure of candidate loci more than SNPs taken alone.
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Genetic testing of epileptic encephalopathies of infancy: an approach.
Sharma, S, Prasad, AN
The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques. 2013;(1):10-6
Abstract
The epileptic encephalopathies of infancy are a group of disorders characterized by intractable seizures, persistent abnormality of cortical function documented on EEG, and consequently impaired neuro-developmental outcomes. The etiologies vary and include; structural brain malformations, acquired brain insults, and inborn errors of metabolism in the majority of the affected patients. In a proportion of these cases no obvious etiology is identifiable on investigation. Recent advances in molecular diagnostics have led to the discovery of a number of gene defects that may be causal in many epileptic encephalopathies. Identification of the causative mutation is important for prognostic and genetic counseling, and may also carry treatment implications. The recently described genes include; Cyclin-Dependent Kinase-Like 5 gene (CDKL5), Protocadherin 19 (PCDH19), Sodium channel neuronal type 1a subunit gene (SCN1A), Aristaless-Related Homeobox Gene (ARX), and Syntaxin binding protein 1 gene (STXBP1), amongst others. Distinct electro-clinical syndromes are increasingly being identified amongst patients carrying the various mutations. In this review, we outline the approach to clinical evaluation and genetic testing of epileptic encephalopathies in infancy.
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Interaction of PPARG Pro12Ala with dietary fat influences plasma lipids in subjects at cardiometabolic risk.
AlSaleh, A, O'Dell, SD, Frost, GS, Griffin, BA, Lovegrove, JA, Jebb, SA, Sanders, TAB
Journal of lipid research. 2011;(12):2298-2303
Abstract
The PPARγ2 gene single nucleotide polymorphism (SNP) Pro12Ala has shown variable association with metabolic syndrome traits in healthy subjects. The RISCK Study investigated the effect of interaction between genotype and the ratio of polyunsaturated:saturated (P:S) fatty acid intake on plasma lipids in 367 white subjects (ages 30-70 years) at increased cardiometabolic risk. Interaction was determined after habitual diet at recruitment, at baseline after a 4-week high-SFA (HS) diet, and after a 24-week reference (HS), high-MUFA (HM), or low-fat (LF) diet. At recruitment, there were no significant associations between genotype and plasma lipids; however, P:S × genotype interaction influenced plasma total cholesterol (TC) (P = 0.02), LDL-cholesterol (LDL-C) (P = 0.002), and triglyceride (TG) (P = 0.02) concentrations. At P:S ratio ≤ 0.33, mean TC and LDL-C concentrations in Ala12 allele carriers were significantly higher than in noncarriers (respectively, P = 0.003; P = 0.0001). Significant trends in reduction of plasma TC (P = 0.02) and TG (P = 0.002) concentrations occurred with increasing P:S (respectively, ≤0.33 to >0.65; 0.34 to >0.65) in Ala12 allele carriers. There were no significant differences between carriers and noncarriers after the 4-week HS diet or 24-week interventions. Plasma TC and TG concentrations in PPARG Ala12 allele carriers decrease as P:S increases, but they are not dependent on a reduction in SFA intake.
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Gene-environment interactions and susceptibility to metabolic syndrome and other chronic diseases.
Ordovas, JM, Shen, J
Journal of periodontology. 2008;(8 Suppl):1508-13
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Abstract
There is an intrinsic complexity in the pathogenesis of common diseases. The concept of gene-environment interaction is receiving support from emerging evidence coming primarily from studies involving diet and cardiovascular disease (CVD) and its various risk factors. The accumulating evidence shows that common variants at candidate genes for lipid metabolism, inflammation, and obesity are associated with altered plasma levels of classic and new biomarkers of metabolic syndrome and CVD risk. Major contributors to this knowledge have been a series of large population studies containing phenotype-rich databases and dietary information to which genetic data have been added. Although this approach has provided strong evidence supporting the concept of gene-diet interactions modulating CVD risk factors, the strength of the individual effect is very small, and the replication among studies is rather disappointing. Current population studies are starting to incorporate experimental and analytical approaches that could provide more solid and comprehensive results. However, other limitations, such as the size of the populations required to examine higher-level interactions, are still major obstacles to translating this knowledge into practical public health applications. Nevertheless, data from numerous molecular and genetic epidemiological studies provide tantalizing evidence suggesting that gene-environment interactions, i.e., the modulation by a genetic polymorphism of a dietary component effect on a specific phenotype (e.g., cholesterol levels and obesity), can interact in ways that increase the risk for developing chronic disease, including susceptibility to developing the metabolic syndrome. Once further experience is gained from patients and/or individuals at high risk, more personalized genetic-based approaches may be applied toward the primary prevention and treatment of CVDs and other complex inflammatory diseases.