The (FTO) gene polymorphism is associated with metabolic syndrome risk in Egyptian females: a case- control study

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Abstract

Background

Variations within fat mass and obesity associated ( FTO) gene had crosstalk with obesity risk in European and some Asian populations. This study was designed to investigate FTO rs9939609 association with metabolic syndrome (MetS) as well as biochemical parameters as plasma glucose, serum triacylglycerol (TAG), total cholesterol (TC) and transaminases enzymes in Arab female population from Egypt.

Methods

In order to achieve that, FTO gene rs9939609 (A < T) was genotyped using TaqMan SNP Genotyping Assay in a total of 197 females which were enrolled in this study. Fasting levels of serum insulin, lipid profile and plasma glucose, in addition to liver transaminases were measured. The association between the genotype distribution and MetS risk was evaluated using Chi-square and logistic regression tests in a case-control design under different genetic models.

Results

The association of genotype distribution with MetS was significant (χ2 = 8.6/ P = 0.014) with an increased odds ratio under dominant model (OR = 1.97, P = 0.029 and 95%C. I = 1.07–3.6) and recessive model (OR = 2.95, P = 0.017 and 95%C. I = 1.22–7.22). Moreover, (AA) subjects showed significant lower HDL-C levels ( P = 0.009) when compared to (TT) ones. In addition, interestingly subjects with (AA) genotype have significantly higher ALT levels ( P = 0.02) that remained significant after correction of major confounders as body mass index and serum triacylglycerols but not after conservative Bonferroni adjustment.

Conclusions

The present study shows for first time that FTO gene rs9939609 is genetic risk factor for metabolic syndrome in Egyptian population which may help in understanding the biology of this complex syndrome and highlighted that this association may be through HDL-C component. The association of this genetic polymorphism with ALT levels needs to be studied in other populations with larger sample size.

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Most cited references 42

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Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans.

S Nambi, K Mather, A. Katz … (2000)

Insulin resistance plays an important role in the pathophysiology of diabetes and is associated with obesity and other cardiovascular risk factors. The "gold standard" glucose clamp and minimal model analysis are two established methods for determining insulin sensitivity in vivo, but neither is easily implemented in large studies. Thus, it is of interest to develop a simple, accurate method for assessing insulin sensitivity that is useful for clinical investigations. We performed both hyperinsulinemic isoglycemic glucose clamp and insulin-modified frequently sampled iv glucose tolerance tests on 28 nonobese, 13 obese, and 15 type 2 diabetic subjects. We obtained correlations between indexes of insulin sensitivity from glucose clamp studies (SI(Clamp)) and minimal model analysis (SI(MM)) that were comparable to previous reports (r = 0.57). We performed a sensitivity analysis on our data and discovered that physiological steady state values [i.e. fasting insulin (I(0)) and glucose (G(0))] contain critical information about insulin sensitivity. We defined a quantitative insulin sensitivity check index (QUICKI = 1/[log(I(0)) + log(G(0))]) that has substantially better correlation with SI(Clamp) (r = 0.78) than the correlation we observed between SI(MM) and SI(Clamp). Moreover, we observed a comparable overall correlation between QUICKI and SI(Clamp) in a totally independent group of 21 obese and 14 nonobese subjects from another institution. We conclude that QUICKI is an index of insulin sensitivity obtained from a fasting blood sample that may be useful for clinical research.

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The obesity-associated FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase.

Thomas Gerken, Christophe A J Girard, Yi-Chun Tung … (2007)

Variants in the FTO (fat mass and obesity associated) gene are associated with increased body mass index in humans. Here, we show by bioinformatics analysis that FTO shares sequence motifs with Fe(II)- and 2-oxoglutarate-dependent oxygenases. We find that recombinant murine Fto catalyzes the Fe(II)- and 2OG-dependent demethylation of 3-methylthymine in single-stranded DNA, with concomitant production of succinate, formaldehyde, and carbon dioxide. Consistent with a potential role in nucleic acid demethylation, Fto localizes to the nucleus in transfected cells. Studies of wild-type mice indicate that Fto messenger RNA (mRNA) is most abundant in the brain, particularly in hypothalamic nuclei governing energy balance, and that Fto mRNA levels in the arcuate nucleus are regulated by feeding and fasting. Studies can now be directed toward determining the physiologically relevant FTO substrate and how nucleic acid methylation status is linked to increased fat mass.

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Is Open Access

Hardy-Weinberg Equilibrium Testing of Biological Ascertainment for Mendelian Randomization Studies

Santiago Rodríguez-Pérez, Tom Gaunt, Ian N M Day (2009)

Mendelian randomization (MR) permits causal inference between exposures and a disease. It can be compared with randomized controlled trials. Whereas in a randomized controlled trial the randomization occurs at entry into the trial, in MR the randomization occurs during gamete formation and conception. Several factors, including time since conception and sampling variation, are relevant to the interpretation of an MR test. Particularly important is consideration of the “missingness” of genotypes that can be originated by chance, genotyping errors, or clinical ascertainment. Testing for Hardy-Weinberg equilibrium (HWE) is a genetic approach that permits evaluation of missingness. In this paper, the authors demonstrate evidence of nonconformity with HWE in real data. They also perform simulations to characterize the sensitivity of HWE tests to missingness. Unresolved missingness could lead to a false rejection of causality in an MR investigation of trait-disease association. These results indicate that large-scale studies, very high quality genotyping data, and detailed knowledge of the life-course genetics of the alleles/genotypes studied will largely mitigate this risk. The authors also present a Web program (http://www.oege.org/software/hwe-mr-calc.shtml) for estimating possible missingness and an approach to evaluating missingness under different genetic models.

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Author and article information

Contributors

Mina S. Khella: minasaad@pharma.asu.edu.eg

Nadia M. Hamdy: nadia_hamdy@pharma.asu.edu.eg

Ashraf I. Amin: ashraf@mailup.net

Hala O. El-Mesallamy: +201061669913 , hala_elmosalamy@hotmail.com

Journal

Journal ID (nlm-ta): BMC Med Genet

Journal ID (iso-abbrev): BMC Med. Genet

Title: BMC Medical Genetics

Publisher: BioMed Central (London )

ISSN (Electronic): 1471-2350

Publication date (Electronic): 16 September 2017

Publication date PMC-release: 16 September 2017

Publication date Collection: 2017

Volume: 18

Electronic Location Identifier: 101

Affiliations

[1 ]ISNI 0000 0004 0621 1570, GRID grid.7269.a, Biochemistry Department, Faculty of Pharmacy, , Ain Shams University, African Union Organization Street, ; Abbassia, Cairo, 11566 Egypt

[2 ]Clinical Pathology and Laboratory Department, National Institute of Diabetes and Endocrinology (NIDE), Cairo, Egypt

Article

Publisher ID: 461

DOI: 10.1186/s12881-017-0461-0

PMC ID: 5603034

PubMed ID: 28915859

SO-VID: 30724c55-edf5-44e6-9f84-93ec3ca911b4

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 25 June 2017

Date accepted : 8 September 2017

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ScienceOpen disciplines: Genetics

Keywords: fto,obesity,snp,t2dm,alt,hdl-c,metabolic syndrome,serum lipids

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ScienceOpen disciplines: Genetics

Keywords: fto, obesity, snp, t2dm, alt, hdl-c, metabolic syndrome, serum lipids

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The ( FTO) gene polymorphism is associated with metabolic syndrome risk in Egyptian females: a case- control study

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Karger: Nutrition and Dietetics

Most cited references 42

Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans.

The obesity-associated FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase.

Hardy-Weinberg Equilibrium Testing of Biological Ascertainment for Mendelian Randomization Studies

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Cited by 13

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