Single nucleotide polymorphism rs7908486 of the TCF7L2 gene is highly associated with obesity in the Iraqi population
Keywords:Obesity, TCF7L2, gene polymorphism, SNP, rs11196208, rs7908486
- Polymorphism of the transcription factor 7-like 2 (TCF7L2) gene is closely associated with increased risk of diabetes mellitus , but its precise role in obesity remains unclear.
- Genotyping of TCF7L2 demonstrated noticeable variation of the rs7908486 SNP in Iraqi adults.
- A risk factor associated with allele A and obesity was observed: individuals with the AA genotype had a higher body mass index, waist circumference, fasting blood glucose and insulin values than individuals with AG and GG genotypes.
- This TCF7L2 gene variation that correlates with obesity can serve as a marker for obesity-related parameters in Iraqi individuals.
Abstract: This study was conducted to assess the possible association between polymorphisms of the transcription factor 7-like 2 (TCF7L2) gene and obese Iraqi adults. DNA was obtained from 158 obese subjects and 142 controls. Two specific PCR fragments were designed to incorporate two highly frequent single nucleotide polymorphism (SNP)s within TCF7L2, rs11196208 and rs7908486. Both amplified loci were genotyped by PCR-single-strand conformation polymorphism (SSCP) followed by sequencing. Logistic regression analysis was performed to detect the association between both genetic variants and obesity. Concerning rs11196208-based amplicons, PCR-SSCP genotyping showed homogeneous banding patterns for all investigated samples. In contrast with rs11196208, three SSCP banding patterns in the rs7908486-based amplicons, GG, AG and AA, were observed. Individuals with the AA genotype showed significantly higher (P<0.05) body mass index (BMI), waist circumference (WC), fasting blood glucose (FBG), and insulin values than those with either AG or GG genotypes. Association analysis revealed that individuals with the A allele exhibited a greater risk of obesity than individuals with the B allele. Data indicate that rs7908486 SNP exerted a tight association with obesity. The study suggests implementing TCF7L2 rs7908486-based genotyping in the early detection of obesity.
Wang DX, Kaur Y, Alyass A, Meyre D. A Candidate-Gene Approach Identifies Novel Associations Between Common Variants in/Near Syndromic Obesity Genes and BMI in Pediatric and Adult European Populations. Diabetes. 2019;68(4):724-32.
Redondo MJ, Steck AK, Sosenko J, Anderson M, Antinozzi P, Michels A, Wentworth JM, Atkinson MA, Pugliese A, Geyer S Transcription factor 7-like 2 (TCF7L2) gene polymorphism and progression from single to multiple autoantibody positivity in individuals at risk for type 1 diabetes. Diabetes Care. 2018;41(12):2480-6.
Vural HC. Tcf7l2 gene polymorphism in T2dm with patients in Turkish population. J Clin Epigenet. 2017;3(3):27.
Hansson O, Zhou Y, Renström E, Osmark P. Molecular function of TCF7L2: Consequences of TCF7L2 splicing for molecular function and risk for type 2 diabetes. Curr Diabetes Rep. 2010;10(6):444-51.
Chen X, Ayala I, Shannon C, Fourcaudot M, Acharya NK, Jenkinson CP, Heikkinen S, Norton L. The diabetes gene and Wnt pathway effector TCF7L2 regulates adipocyte development and function. Diabetes. 2018;67(4):554-68.
Lyssenko V, Lupi R, Marchetti P, Del Guerra S, Orho-Melander M, Almgren P, Sjögren M, Ling C, Eriksson KF, Lethagen AL, Mancarella R, Berglund G, Tuomi T, Nilsson P, Del Prato S, Groop L. Mechanisms by which common variants in the TCF7L2 gene increase risk of type 2 diabetes. J Clin Invest. 2007;117(8):2155-63.
Gonzalez-Sanchez JL, Martinez-Larrad MT, Zabena C, Perez-Barba M, Serrano-Rios M. Association of variants of the TCF7L2 gene with increases in the risk of type 2 diabetes and the proinsulin: insulin ratio in the Spanish population. Diabetologia. 2008;51(11):1993-7.
Alami FM, Ahmadi M, Bazrafshan H, Tabarraei A, Khosravi A, Tabatabaiefar MA, Samaei NM. Association of the TCF7L2 rs12255372 (G/T) variant with type 2 diabetes mellitus in an Iranian population. Genet Mol Biol. 2012;35(2):413-7.
Velayutham K, Ramanathan B, Murugan J, Murugan A, Thavamani V, Gomathinayagam R. Carriers of the TCF7L2 rs7903146, rs12255372 risk alleles in the south Tamil Nadu T2DM patients present with early incidence and insulin dependence. Indian J Endocrinol Metab. 2019;23(5):563.
Wrzosek M, Sawicka A, Wrzosek M, Piątkiewicz P, Tałałaj M, Nowicka G. Age at onset of obesity, transcription factor 7-like 2 (TCF7L2) rs7903146 polymorphism, adiponectin levels and the risk of type 2 diabetes in obese patients. Arch Med Sci. 2019;15(2):321.
Li L, Wang J, Ping Z, Li Y, Wang C, Shi Y, hou W, Zhang L. Interaction analysis of gene variants of TCF7L2 and body mass index and waist circumference on type 2 diabetes. Clin Nutr. 2020;39(1):192-7.
Weiderpass E, Botteri E, Longenecker JC, Alkandari A, Al-Wotayan R, Al Duwairi Q, Tuomilehto J. The prevalence of overweight and obesity in an adult Kuwaiti population in 2014. Front Endocrinol. 2019;10:449.
Pengpid S, Peltzer K. Overweight and obesity among adults in Iraq: Prevalence and correlates from a national survey in 2015. medRxiv 2020110489 [Preprint]. 2020 [cited 2020 Nov 18]. Available from:https://doi.org/10.20944/preprints202011.0489.v1
Zhang X, Xu S, Gao X, Zhang L, Ren H, Chen J. The application of asymmetric PCR-SSCP in gene mutation detecting. Front Agric China. 2008;2(3):361-4.
Seimon R V, Wild-Taylor AL, Gibson AA, Harper C, McClintock S, Fernando HA, Hsu MSH, Luz FQD, Keating SE, Johnson NA, Grieve SM, Markovic TP, Caterson ID, Byrne NM, Sainsbury A. Less waste on waist measurements: determination of optimal waist circumference measurement site to predict visceral adipose tissue in postmenopausal women with obesity. Nutrients. 2018;10(2):239.
Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972;18(6):499-502.
Al-Shuhaib MBSA. A universal, rapid, and inexpensive method for genomic DNA isolation from the whole blood of mammals and birds. J Genet. 2017;96(1):171-176.
Ye J, Coulouris G, Zaretskaya I, Cutcutache I, Rozen S, Madden TL. Primer-BLAST: a tool to design target-specific primers for polymerase chain reaction. BMC Bioinformatics. 2012;13(1):134.
Hashim HO, Al-Shuhaib MBS. Exploring the potential and limitations of PCR-RFLP and PCR-SSCP for SNP detection: A review. J Appl Biotechnol Rep. 2019;6(4):137-44.
Al-Shuhaib MBS, Al-Thuwaini TM, Fadhil IA, Aljubouri TRS. GHRL gene-based genotyping of ovine and caprine breeds reveals highly polymorphic intronic sequences in Awassi sheep with several RNA motifs. J Genet Eng Biotechnol. 2019;17(1).
Byun SO, Fang Q, Zhou H, Hickford JGH. An effective method for silver-staining DNA in large numbers of polyacrylamide gels. Anal Biochem. 2009;385(1):174-5.
Yeh FC, Yang RC. POPGENE version 1.31, Microsoft window-based freeware for population genetic analysis. University of Alberta and Tim Boyle, Centre for International Forestry Research. ftp microsoft com/softlib/slfiles/hpgl exe. 1999;
Huang Z, Liao Y, Huang R, Chen J, Sun H. Possible role of TCF7L2 in the pathogenesis of type 2 diabetes mellitus. Biotechnol Biotec Eq. 2018;32(4):830-4.
Petermann-Rocha F, Lasserre-Laso N, Villagrán M, Mardones L, Martínez MA, Leiva AM, Ulloa N, Celis-Morales C. Association of the TCF7L2 (RS7903146) genotype with adiposity and metabolic markers in the Chilean adult population. Rev Med Chile. 2019;147(8):965-76.
Khan SM, El Karte N, El Hajj Chehadeh S, Hassoun A, Afandi B, Tay GK, Alsafar H. Association between type 2 diabetes mellitus & TCF7L2 gene variants in the Emirati population: Genetics of diabetes in the United Arab Emirates. Am J Hum Biol. 2020;e23434.
Morgan MF, Salam RF, Rady NH, Alnaggar ARLR, Ammar SH, Ghanem NS. The Association of Transcription Factor 7 like 2 Gene Polymorphism with Diabetic Nephropathy in Patients with Type 2 Diabetes Mellitus. Curr Diabetes Rev. 2020;16(4):370-5.
Buzdugan L, Kalisch M, Navarro A, Schunk D, Fehr E, Bühlmann P. Assessing statistical significance in multivariable genome wide association analysis. Bioinformatics. 2016;32(13):1990-2000.
Haupt A, Thamer C, Heni M, Ketterer C, Machann J, Schick F, Machicao F, Stefan N, Claussen CD, Häring HU, Fritsche A, Staiger H. Gene variants of TCF7L2 influence weight loss and body composition during lifestyle intervention in a population at risk for type 2 diabetes. Diabetes. 2010;59(3):747-50.
Bodhini D, Gaal S, Shatwan I, Ramya K, Ellahi B, Surendran S, Sudha V, Anjana MR, Mohan V, Lovegrove JA, Radha V, Vimaleswaran KS. Interaction between TCF7L2 polymorphism and dietary fat intake on high density lipoprotein cholesterol. PloS One. 2017;12(11):e0188382.
Guewo-Fokeng M, Sobngwi E, Atogho-Tiedeu B, Donfack OS, Noubiap JJN, Ngwa EN, Mato-Mofo EP, Fosso PP, Djahmeni E, Djokam-Dadjeu R, Evehe MS, Aminkeng F, Mbacham WF, Mbanya JC. Contribution of the TCF7L2 rs7903146 (C/T) gene polymorphism to the susceptibility to type 2 diabetes mellitus in Cameroon. J Diabetes Metab Disord. 2015;14(1):26.
Biyasheva A, Legro RS, Dunaif A, Urbanek M. Evidence for association between polycystic ovary syndrome (PCOS) and TCF7L2 and glucose intolerance in women with PCOS and TCF7L2. J Clin Endocrinol Metab. 2009;94(7):2617-25.
Nguimmo-Metsadjio A, Atogho-Tiedeu B, Noubiap JJ, Evehe M-S, Djokam-Dadjeu R, Donfack OS, Nanfa D, Mato EPM, Ngwa EN, Guewo-Fokeng M, Pokam-Fosso P, Mbacham WF, Mbanya JC, Sobngwi E. Investigation of the association between the TCF7L2 rs7903146 (C/T) gene polymorphism and obesity in a Cameroonian population: a pilot study. J Health Popul Nutr. 2017;36(1):12.
Ramos-Lopez O, Riezu-Boj JI, Milagro FI, Cuervo M, Goni L, Martinez JA. Interplay of an Obesity-Based Genetic Risk Score with Dietary and Endocrine Factors on Insulin Resistance. Nutrients. 2020;12(1):33.
How to Cite
Copyright (c) 2021 Archives of Biological Sciences
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
Authors grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution 4.0 International License that allows others to share the work with an acknowledgment of the work’s authorship and initial publication in this journal.