Association of the Gene FTO Single Nucleotide Polymorphism, rs9939609 with Type 2 Diabetes Mellitus in Pakistani Cohort

Authors

  • Afira Waqar Institute of Industrial Biotechnology, Government College University, Lahore, Pakistan
  • Bushra Chaudhry Department of Biosciences, Salim Habib University, Karachi, Pakistan
  • Ikram-ul Haq Institute of Industrial Biotechnology, Government College University, Lahore, Pakistan
  • Ali Nawaz Pakistan Academy of Sciences Islamabad, Pakistan

DOI:

https://doi.org/10.53560/PPASB(60-2)871

Keywords:

Genome-Wide Association Studies, Type 2 Diabetes Mellitus, Single Nucleotide Polymorphism, Fat mass and obesity-associated gene

Abstract

To date, inconclusive data is available about the insight of the FTO gene variant with type 2 diabetes mellitus. T2DM is a chronic disease and a rising problem worldwide. Its complications lead to an increase in the burden of mortality specifically in lower and medium-income countries. Genome-wide association studies have spotted many genetic loci that are related to T2DM and validate the complicated polygenic traits. Many variants of different genes including FTO are associated with T2DM hence, this study was designed to inspect and unfold obscure data in South Asians. The main objective of present study is to identify the relation of FTO intronic variant rs9939609 with T2DM in Karachi-based Sindhi population of Pakistan. Total recruited individuals were grouped as diabetic cases and controls. Out of the total recruited subjects, genotyping was done on 152 samples using T-ARMS PCR however, demographic and clinical data were recorded of all individuals. The results showed that the frequency of variant genotypes in the diabetic case group was 11 % for AA, 45 % for AT and 44 % for TT though, the frequency of the lethal allele (T) was 34 %. These outcomes concluded, rare T allele frequency is higher among diabetic cases as compared to controls and provides the contribution from the Pakistani population to support the previous controversial findings. This study concluded FTO gene-single nucleotide polymorphism, rs9939609 is associated with T2DM but still, it is a growing need to do further studies on T2DM susceptible genes with different polymorphisms to recognize targets in the field of pharmacogenomics for clinical implementation.

References

World Health Organization. Classification of Diabetes Mellitus 2019; World Health Organization. Available online: https://apps.who.int/iris/handle/10665/325182 (accessed on 5 January 2020).

J.E. Shaw, R.A. Sicree and P.Z. Zimmet. Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes research and clinical practice 87(1): 4–14 (2010).

International Diabetes Federation. IDF Diabetes Atlas, 9th edn. Brussels, Belgium: International Diabetes Federation, 2019.

P. Rajendra and V. Mohan. Epidemiology of type 2 diabetes in India. Indian journal of ophthalmology 69: 2932-2938 (2021).

E.R. Pulgaron, and A.M Delamater. Obesity and type 2 diabetes in children: epidemiology and treatment. Current diabetes reports 14(8): 508 (2014).

A. Angi, and F. Chiarelli. Obesity and Diabetes: A Sword of Damocles for Future Generations. Biomedicines 8(11): 478 (2020).

D.R Leitner, G. Frühbeck, V. Yumuk, K. Schindler, D. Micic, E. Woodward and H. Toplak, H. Obesity and Type 2 Diabetes: Two Diseases with a Need for Combined Treatment Strategies - EASO Can Lead the Way. Obesity facts 10(5): 483–492 (2017).

P.A. Dyson. The therapeutics of lifestyle management on obesity. Diabetes, obesity & metabolism12(11): 941–946 (2010).

N.M. Varda, M. Medved and L. Ojsteršek. The associations between some biological markers, obesity, and cardiovascular risk in Slovenian children and adolescents. BMC Pediatr 20: 81 (2020).

D. Ağagündüz and M. GEZmen-Karadağ. Association of FTO common variant (rs9939609) with body fat in Turkish Chinese individuals. Lipids Health Dis 18: 212 (2019).

A. Kar, M.A. Munim, A. Fariha, A.S. Roy, M.I. Rahman, S. Akter, M.I.Q. Tonmoy, M.R. Alam, A.I.B. Raunak, S. Selim, M.M. Hossain, H.A. Reza, N.M. Bahadur and M.S. Hossain. Association of an intronic SNP rs9939609 in FTO gene with type 2 diabetes mellitus among Bangladeshi population: A case–control study combined with updated meta-analysis. Human Gene 35 (2023). https://doi.org/10.1016/j.humgen.2022.201133.

S. Khan, A.K. Verma, V. Khan, D. Bhatt, M.A. Alsahli, A.H. Rahmani, B. Meena, I.H. Naqvi and K. Dev. Role of FTO and MC4R Polymorphisms in Escalating Obesity and Their Indirect Association With Risk of T2D in Indian Population. Diabetes Ther 11: 2145–2157 (2020).

A. Waqar, B. Chaudhry, I. Haq, K. Saboohi and M.N. Aftab. Association between type 2 diabetes mellitus and TCF7L2 gene variant in the Pakistani cohort. Int J Diabetes Dev Ctries (2022). https://doi.org/10.1007/s13410-022-01138-4

O.E. Osayande, G. N. Azekhumen, and E.O Obuzor. A Comparative Study of different body fat measuring instruments. Nigerian journal of physiological sciences: official publication of the Physiological Society of Nigeria 33(2): 125–128 (2018).

WHO. WHO STEPwise approach to surveillance (STEPS). Geneva, World Health Organization (WHO), 2008b.

A.S. Vischer and T. Burkard. Principles of Blood Pressure Measurement - Current Techniques, Office vs Ambulatory Blood Pressure Measurement. Advances in experimental medicine and biology 956: 85–96 (2017).

S. Bakhashab, N. Filimban, R.M. Altall, R. Nassir, S.Y. Qusti, M.H. Alqahtani, A.M. Abuzenadah and A. Dallol. The Effect Sizes of PPARγ rs1801282, FTO rs9939609, and MC4R rs2229616 Variants on Type 2 Diabetes Mellitus Risk among the Western Saudi Population: A Cross-Sectional Prospective Study. Genes 11(1): 98 (2020).

C.S. Yajnik C.S. Janipalli, S. Bhaskar, S.R. Kulkarni, R.M. Freathy and S. Prakash. FTO gene variants are strongly associated with type 2 diabetes in South Asian Indians. Diabetologia 52:247–252 (2009).

D.K. Sanghera, L. Ortega, S. Han, J. Singh, S.K. Ralhan and G.S. Wander. Impact of nine common type 2 diabetes risk polymorphisms in Asian Indian Sikhs: PPARG2 (Pro12Ala), IGF2BP2, TCF7L2 and FTO variants confer a significant risk. BMC Med Genet 9:59 (2008).

E.G. García-Chapa, E. Leal-Ugarte, V. Peralta-Leal, J. Durán-González and J.P. Meza-Espinoza. Genetic Epidemiology of Type 2 Diabetes in Mexican Mestizos. BioMed research international 3937893 (2017).

A. Sabarneh, S. Ereqat, S Cauchi, O. AbuShamma, M. Abdelhafez, M. Ibrahim and A. Nasereddin. Common FTO rs9939609 variant and risk of type 2 diabetes in Palestine. BMC medical genetics 19(1): 156 (2018).

A. Boles, R. Kandimalla and P.H. Reddy. Dynamics of diabetes and obesity: Epidemiological perspective. Biochimica et biophysica acta. Molecular basis of disease 1863(5), 1026–1036 (2017).

B. Xi, Y. Shen, M. Zhang, X. Liu, X. Zhao, L. Wu, H. Cheng, D. Hou, K. Lindpaintner, L. Liu, J. Mi and X. Wang. The common rs9939609 variant of the fat mass and obesity-associated gene is associated with obesity risk in children and adolescents of Beijing,

China. BMC medical genetics 11: 107 (2010).

T.M. Frayling, N.J. Timpson, M.N. Weedon, E. Zeggini, R.M. Freathy, C.M. Lindgren, J.R. Perry, K.S. Elliott, H. Lango, N.W. Rayner, B. Shields, L.W. Harries, J.C. Barrett, S. Ellard, C.J. Groves, B. Knight, A.M. Patch, A.R. Ness, S. Ebrahim, D.A. Lawlor and M.J. McCarthy. A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science

(New York, N.Y.) 316(5826): 889–894 (2007).

Y.C. Chang, P.H. Liu, W.J. Lee, T.J. Chang, Y.D Jiang, H.Y. Li, S.S. Kuo, K.C. Lee and L.M. Chuang. Common variation in the fat mass and obesityassociated (FTO) gene confers risk of obesity and modulates BMI in the Chinese population. Diabetes 57(8): 2245–2252 (2008).

T.Q. Binh, P.T. Phuong, B.T. Nhung, D.D. Thoang, H.T. Lien and D.V. Thanh. Association of the common FTO-rs9939609 polymorphism with type 2 diabetes, independent of obesity-related traits in a Vietnamese population. Gene 513(1), 31–35 (2013).

B. Xi, J. Mi. FTO polymorphisms are associated with obesity but not with diabetes in East Asian populations: a meta-analysis. Biomed Environ Sci 22: 449–457 (2009).

G. Chauhan, R. Tabassum, A. Mahajan, O.P. Dwivedi, Y. Mahendran, I. Kaur, S. Nigam, H. Dubey, B. Varma, S.V. Madhu, S.K. Mathur, S. Ghosh, N. Tandon and D. Bharadwaj. Common variants of FTO and the risk of obesity and type 2 diabetes in

Indians. Journal of human genetics 56(10), 720–726 (2011).

Binh, T.Q., Linh, D.T., Chung, L.T.K. et al. FTO-rs9939609 Polymorphism is a Predictor of Future Type 2 Diabetes: A Population-Based Prospective Study. Biochem Genet 60, 707–719 (2022). https://doi.org/10.1007/s10528-021-10124-0

Q. Qi, T.O. Kilpeläinen, M.K. Downer, T. Tanaka, C.E. Smith, I. Sluijs. E. Sonestedt, A.Y. Chu, F. Renström, X. Lin, L.H. Ängquist, J. Huang, Z. Liu, Y. Li, P. Chen, M. Daimon and L. Qi. FTO genetic variants, dietary intake and body mass

index: insights from 177,330 individuals. Hum Mol Genet 23(25):6961-6972 (2014).

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Published

2023-05-27

How to Cite

Afira Waqar, Bushra Chaudhry, Ikram-ul Haq, & Ali Nawaz. (2023). Association of the Gene FTO Single Nucleotide Polymorphism, rs9939609 with Type 2 Diabetes Mellitus in Pakistani Cohort. Proceedings of the Pakistan Academy of Sciences: B. Life and Environmental Sciences, 60(2), 143–150. https://doi.org/10.53560/PPASB(60-2)871

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Research Articles