Role of Roof plate-specific SPONDIN3 Mutation in the Determination of Obesity Phenotypes/Fat Distribution and Susceptibility to Cardiovascular disease in Sudanese Patients in Khartoum State
Background: Obesity is a major risk factor for the development of cardiovascular disease. A growing database of clinical evidence implicates intra-abdominal adiposity as a powerful driving force for elevated cardiometabolic risk (1). Addressing intra-abdominal adiposity should play a central role in future strategies aimed at improving cardiovascular outcomes in patients with abdominal obesity and its associated cardiometabolic risk in Sudan.
Objectives: It is to find the mutation in R-SPONDIN3gene and its association to both of fat deposition around the abdomen and susceptibility to cardiovascular disease in Sudanese patients in Khartoum State.
Material and methods: Conventional PCR was done to detect R- SPONDIN3 in 300 participants (males and females) classified into three groups. The first group will include one hundred participants with abdominal obesity, the second group will include one hundred participants already diagnosed with CVD entangled with obesity (positive control group), while the third group will include one hundred healthy lean volunteers (negative control group). Data was analyzed using SPSS Version 22 software. P value < 0.05 was considered as statistically significant.
Results: In this study, the results of Conventional PCR were significantly different in (P <0.001) in Heart group subjects as compared to healthy controls and obese group. Comparison between the different studied groups according to gene expression showed significant differences (P <0.001) mean value of gene expression in healthy group subjects was 1.0 ± 0.0, Obesity group was 2.44 ± 0.50 and heart group subjects was 4.54 ± 0.87 respectively .
Conclusion: clinically, detect R- SPONDIN3 mutation in patients with diagnosed with CVD entangled with obesity and amount of the gene expressed cleared different between obese and CVD subjects entangled with obesity.
Keywords: R-SPONDIN3 gene, abdominal Obesity, CVD.
2. D'agostino, R.B.,Vasan, R.S.,Pencina, M.J. General Cardiovascular Risk Profile For Use Inprimary Care: The Framingham Heart Study. Circulation; 2008; 117:743-53.
3. H E Bays, J M González-Campoy, R R Henry, D A Bergman, A E Kitabchi,A B Schorr,And H W Rodbard; Is Adiposopathy (Sick Fat) An Endocrine Disease?;Int J Clin Pract. 2008; 62(10):1474–1483. Doi: 10.1111/J.1742-1241.2008.01848.X.
4. YUSUF, S., HAWKEN, S., OUNPUU, S. Obesity And The Risk Of myocardial infarction in 27,000 participants from 52 countries: a case-control study: Lancet. 2005; 366:1640-9.
5. JANSSEN, I., MARK, A.E. Elevated body mass index and mortality risk in the elderly: Obes Rev, 2007; 8:41-59.
6. MCLAUGHLIN, T., LAMENDOLA, C., LIU, A., ABBASI, F. Preferential Fat Deposition in Subcutaneous Versus Visceral Depots Is Associated with Insulin Sensitivity: PubMed. 2011 ; 60 -65.
7. NISHIDA, C. Appropriate body-mass index for Asian populations and its implications forpolicy and intervention strategies: Lancet; 2004; 902.
8. Poehlman, Eric T. "Abdominal Obesity: The Metabolic Multi-risk Factor". Coronary Heart Disease. Exp. 2010; 9(8):469–471. doi:10.1097/00019501-199809080-00001.
9. Speliotes EK, Willer CJ, Berndt SI, Monda KL, Thorleifsson G, Jackson AU, Allen HL, Lindgren CM, Luan J, Mägi R, Randall JC, Vedantam S, Winkler TW, Qi L, Workalemahu T, Heid IM, Steinthorsdottir V, Stringham HM, Weedon MN, Wheeler E, Wood AR, Ferreira T, Weyant RJ, Segrè AV, Estrada K, Liang L, Nemesh J, Park JH, Gustafsson S, Kilpeläinen TO. et al. Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index. Nat Genet. 2010; 42:937–948. doi: 10.1038/ng.686.
10. Carmon KS, Gong X, Lin Q, Thomas A, Liu Q, R-spondins function as ligands of the orphan receptors LGR4 and LGR5 to regulate Wnt/betacatenin signaling. Proc Natl Acad Sci U S A 2011; 108(28):11452-11457.
11. N.Y. Loh1 , K.E. Pinnick1 , J.E.N. Minchin2 , M.J. Neville1,3, J.F. Rawls2 , F. Karpe1,3.C RSPO3 functions via LGR4 to regulate human body fat distribution by eliciting diverse biological responses in abdominal and gluteal progenitors. ". Endocrine. 2013; 46:231–240.
12. Dorit Schleinitz, Yvonne Böttcher, Matthias Blüher, Peter Kovacs .The genetics of fat distribution . Diabetologia, 2014; 57(7):1276.
13. Michael M. Mendelson, Riccardo E. Marioni,Roby Joehanes, Chunyu Liu,Åsa K. Hedman, Stella Aslibekyan,Ellen W. Demerath, Weihua Guan, Degui Zhi, Chen Yao, Tianxiao Huan, Christine Willinger, Brian Chen, Paul Courchesne, Michael Multhaup, Marguerite R. Irvin,11 Ariella Cohain, Eric E. Schadt, Megan L. Grove, Jan Bressler, Kari North, Johan Sundström, Stefan Gustafsson, . Association of Body Mass Index with DNA Methylation and Gene Expression in Blood Cells and Relations to Cardiometabolic Disease: A Mendelian Randomization Approach. 2017 Jan 17.
14. Rajiv Gandhi, MS, Herman Dhotar, , Dmitry Tsvetkov, and Nizar N. Mahomed. The relation between body mass index and waist–hip ratio in knee osteoarthritis. 2010; 53(3):151–153.
15. Kalypso Karastergiou, Steven R Smith, Andrew S Greenberg, and Susan K Fried. Sex differences in human adipose tissues – the biology of pear shape. 2012 May 31. doi: 10.1186/2042-6410-3-13.
16. Atzmon, G.; Yang, X. M.; Muzumdar, R.; Ma, X. H.; Gabriely, I.; Barzilai, N. "Differential Gene Expression between Visceral and Subcutaneous Fat Depots". Hormone and Metabolic Research. 2002; 34(11/12):622–628.
17. Ian J. Neeland, Colby R. Ayers, Anand K. Rohatgi, Aslan T. Turer, Jarett D. Berry, Sandeep R. Das, Gloria L. Vega, Amit Khera, Darren K. McGuire, Scott M. Grundy, and James A. de Lemos . Associations of visceral and abdominal subcutaneous adipose tissue with markers of cardiac and metabolic risk in obese adults. 2013 May 19. doi: 10.1002/oby.20135
18. Tobin M. Abraham , Alison Pedley , Joseph M. Massaro , Udo Hoffmann , and Caroline S. Fox . Association between Visceral and Subcutaneous Adipose Depots and Incident Cardiovascular Disease Risk Factors . Aug 2015; 132(17):1639–1647.
19. Adamska M, Billi AC, Cheek S, Meisler MH. Genetic interaction between Wnt7a and Lrp6 during patterning of dorsal and posterior structures of the mouse limb. Dev Dyn. 2005; 233:368–372. doi: 10.1002/dvdy.20437.
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