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Erschienen in: International Journal of Diabetes in Developing Countries 2/2019

21.09.2018 | Original Article

Genome-wide implicated risk variants of TCF7L2 gene contribute to type 2 diabetes susceptibility by modulating serum lipids in Pakistani population

verfasst von: Shafiqa Shahzadi, Shabana, Sumbal Sarwar, Saleem Ullah Shahid

Erschienen in: International Journal of Diabetes in Developing Countries | Ausgabe 2/2019

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Abstract

Diabetes is a socioeconomic burden worldwide as well as in Pakistan. International Diabetes Federation reported 7 million cases of diabetes and 86,384 deaths due to diabetes in Pakistan in 2015. Transcription factor 7 like 2 is a transcription factor encoded by TCF7L2 gene and regulates several physiological processes in the cell. The aim of the current study was to determine the prevalence of two TCF7L2 gene polymorphisms and analyze its effect on various anthropometric and biochemical parameters in a Pakistani cohort. We collected 926 samples, 500 healthy controls (fasting blood sugar < 99 mg/dL, random blood sugar < 126 mg/dL) and 426 cases with diabetes (fasting blood sugar > 99 mg/dL, random blood sugar > 126 mg/dL). The genotyping was done by RFLP-PCR and serum biochemical parameters were determined. The genotyping results of rs7903146 by RLFP-PCR showed the allelic frequency of C = 0.64 and T = 0.36 in controls while C = 0.59 and T = 0.41 in cases and genotypic frequency CC = 43.2%, CT = 41.6%, and TT = 15.2% in controls while CC = 34.03%, CT = 49.06%, and TT = 16.91% in cases. The minor T allele appeared to be a risk allele (OR = 1.25, CI = 1.03–1.51, p = 0.016), i.e., it increased the risk of diabetes in the selected study subjects. The genotyping results of rs12255372 showed allelic frequency G = 0.75 and T = 0.25 in controls while G = 0.63 and T = 0.37 in cases and genotypic frequency GG = 54.2%, GT = 42.2%, and TT = 3.6% in controls, while GG = 40.14%, GT = 46.24%, and TT = 13.62% in cases. The minor T allele appeared to be a risk allele for this SNP as well (OR = 1.77, CI = 1.44–2.16, p = 1.9 × 10−8). The biochemical parameters and general characteristics were checked for association with the TCF7L2 variant rs7903146, showed no association with all tested parameters. While rs12255372 had significant association with fasting plasma glucose, triglycerides, HDLC, LDLC, and leptin, but no association with total cholesterol, age, height, weight, and BMI. However, the multivariate analysis showed significant association of lipid parameters only when homozygous risk genotype of rs12255372 co-existed with all genotypes of rs7903146. In conclusion, the polymorphisms in TCF7L2 gene can increase the susceptibility to diabetes and the effect may involve modulating certain serum traits.
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Literatur
1.
Zurück zum Zitat Kaul K, et al. Introduction to diabetes mellitus. In Diabetes. Springer; 2013. p. 1–11. Kaul K, et al. Introduction to diabetes mellitus. In Diabetes. Springer; 2013. p. 1–11.
2.
Zurück zum Zitat Bahadar H, Mostafalou S, Abdollahi M. Growing burden of diabetes in Pakistan and the possible role of arsenic and pesticides. J Diabetes Metab Disord. 2014;13(1):117.CrossRefPubMedPubMedCentral Bahadar H, Mostafalou S, Abdollahi M. Growing burden of diabetes in Pakistan and the possible role of arsenic and pesticides. J Diabetes Metab Disord. 2014;13(1):117.CrossRefPubMedPubMedCentral
4.
Zurück zum Zitat Musavi Z, Azarpira N, Sangtarash MH, Kordi M, Kazemi K, Geramizadeh B, et al. Polymorphism of Transcription Factor-7-Like 2 (TCF7L2) gene and new-onset diabetes after liver transplantation. Int J Organ Transplant Med. 2015;6(1):14–22.PubMedPubMedCentral Musavi Z, Azarpira N, Sangtarash MH, Kordi M, Kazemi K, Geramizadeh B, et al. Polymorphism of Transcription Factor-7-Like 2 (TCF7L2) gene and new-onset diabetes after liver transplantation. Int J Organ Transplant Med. 2015;6(1):14–22.PubMedPubMedCentral
5.
Zurück zum Zitat Lu X, et al. TCF7L2 gene polymorphisms and susceptibility to breast cancer: a meta-analysis. Genet Mol Res. 2015;14(1):2860–7.CrossRefPubMed Lu X, et al. TCF7L2 gene polymorphisms and susceptibility to breast cancer: a meta-analysis. Genet Mol Res. 2015;14(1):2860–7.CrossRefPubMed
6.
Zurück zum Zitat Strom A. Insights into extrinsic and intrinsic signals controlling murine pancreas development, growth and maintenance. University of Geneva; 2007. Strom A. Insights into extrinsic and intrinsic signals controlling murine pancreas development, growth and maintenance. University of Geneva; 2007.
7.
Zurück zum Zitat Olausson J. Studies on microcirculation in insulin resistance. 2015. Olausson J. Studies on microcirculation in insulin resistance. 2015.
8.
Zurück zum Zitat Shah M, Vella A. Understanding diabetes mellitus: pathophysiology, in Metabolic Syndrome and Diabetes, Springer; 2016. p. 33–45. Shah M, Vella A. Understanding diabetes mellitus: pathophysiology, in Metabolic Syndrome and Diabetes, Springer; 2016. p. 33–45.
9.
Zurück zum Zitat Moran Y, et al. Design of an allele-specific PCR assay to genotype the rs12255372 SNP in a pilot study of association between common TCF7L2 polymorphisms and type 2 diabetes in Venezuelans. Archives of Endocrinology and Metabolism(AHEAD). 2015. Moran Y, et al. Design of an allele-specific PCR assay to genotype the rs12255372 SNP in a pilot study of association between common TCF7L2 polymorphisms and type 2 diabetes in Venezuelans. Archives of Endocrinology and Metabolism(AHEAD). 2015.
10.
Zurück zum Zitat Ramos RB et al. Association between rs7903146 and rs12255372 polymorphisms of transcription factor 7-like 2 gene and polycystic ovary syndrome: a systematic review and meta-analysis. Endocrine. 2015:1–8. Ramos RB et al. Association between rs7903146 and rs12255372 polymorphisms of transcription factor 7-like 2 gene and polycystic ovary syndrome: a systematic review and meta-analysis. Endocrine. 2015:1–8.
11.
Zurück zum Zitat Yao H, Wang Z, Wang T, Ma Y, Su Y, Ma Q, et al. Association of TCF7L2 genetic polymorphisms with type 2 diabetes mellitus in the Uygur population of China. Int J Environ Res Public Health. 2015;12(9):11797–814.CrossRefPubMedPubMedCentral Yao H, Wang Z, Wang T, Ma Y, Su Y, Ma Q, et al. Association of TCF7L2 genetic polymorphisms with type 2 diabetes mellitus in the Uygur population of China. Int J Environ Res Public Health. 2015;12(9):11797–814.CrossRefPubMedPubMedCentral
12.
Zurück zum Zitat Khodaeian M, Enayati S, Tabatabaei-Malazy O, Amoli MM. Association between genetic variants and diabetes mellitus in Iranian populations: a systematic review of observational studies. J Diabetes Res. 2015;2015:1–21.CrossRef Khodaeian M, Enayati S, Tabatabaei-Malazy O, Amoli MM. Association between genetic variants and diabetes mellitus in Iranian populations: a systematic review of observational studies. J Diabetes Res. 2015;2015:1–21.CrossRef
13.
Zurück zum Zitat Butt H, Shabana, Hasnain S. The C1431T polymorphism of peroxisome proliferator activated receptor γ (PPARγ) is associated with low risk of diabetes in a Pakistani cohort. Diabetol Metab Syndr. 2016;8(1):67.CrossRefPubMedPubMedCentral Butt H, Shabana, Hasnain S. The C1431T polymorphism of peroxisome proliferator activated receptor γ (PPARγ) is associated with low risk of diabetes in a Pakistani cohort. Diabetol Metab Syndr. 2016;8(1):67.CrossRefPubMedPubMedCentral
14.
Zurück zum Zitat Alami FM, et al. Association of transcription factor 7-like 2 (Tcf7l2) gene haplotypes with the risk of type 2 diabetes mellitus in Iran. Adv Biol Res. 2013;7(5):145–50. Alami FM, et al. Association of transcription factor 7-like 2 (Tcf7l2) gene haplotypes with the risk of type 2 diabetes mellitus in Iran. Adv Biol Res. 2013;7(5):145–50.
15.
Zurück zum Zitat Alami FM, Ahmadi M, Bazrafshan H, Tabarraei A, Khosravi A, Tabatabaiefar MA, et al. 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.CrossRefPubMedPubMedCentral Alami FM, Ahmadi M, Bazrafshan H, Tabarraei A, Khosravi A, Tabatabaiefar MA, et al. 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.CrossRefPubMedPubMedCentral
16.
Zurück zum Zitat Lo C, Ilic D, Teede H, Cass A, Fulcher G, Gallagher M, et al. The perspectives of patients on health-care for co-morbid diabetes and chronic kidney disease: a qualitative study. PLoS One. 2016;11(1):e0146615.CrossRefPubMedPubMedCentral Lo C, Ilic D, Teede H, Cass A, Fulcher G, Gallagher M, et al. The perspectives of patients on health-care for co-morbid diabetes and chronic kidney disease: a qualitative study. PLoS One. 2016;11(1):e0146615.CrossRefPubMedPubMedCentral
17.
Zurück zum Zitat Mutlu F et al. Projection of diabetes burden through 2025 and contributing risk factors of changing disease prevalence: an emerging public health problem. J Diabetes Metab. 2014. Mutlu F et al. Projection of diabetes burden through 2025 and contributing risk factors of changing disease prevalence: an emerging public health problem. J Diabetes Metab. 2014.
18.
Zurück zum Zitat Triplitt C et al. Classification of diabetes mellitus. 2015. Triplitt C et al. Classification of diabetes mellitus. 2015.
19.
Zurück zum Zitat Turner N, Zeng XY, Osborne B, Rogers S, Ye JM. Repurposing drugs to target the diabetes epidemic. Trends Pharmacol Sci. 2016;37(5):379–89.CrossRefPubMed Turner N, Zeng XY, Osborne B, Rogers S, Ye JM. Repurposing drugs to target the diabetes epidemic. Trends Pharmacol Sci. 2016;37(5):379–89.CrossRefPubMed
20.
Zurück zum Zitat Grant SF, et al. Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes. Nat Genet. 2006;38(3):320–3.CrossRefPubMed Grant SF, et al. Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes. Nat Genet. 2006;38(3):320–3.CrossRefPubMed
21.
Zurück zum Zitat Meshram A et al. Correlation of dyslipidemia and type 2 diabetes mellitus amongst the people of Vidarbha region of India. Meshram A et al. Correlation of dyslipidemia and type 2 diabetes mellitus amongst the people of Vidarbha region of India.
22.
Zurück zum Zitat Nemr R, Turki A, Echtay A, al-Zaben GS, Daher HS, Irani-Hakime NA, et al. Transcription factor-7-like 2 gene variants are strongly associated with type 2 diabetes in Lebanese subjects. Diabetes Res Clin Pract. 2012;98(3):e23–7.CrossRefPubMed Nemr R, Turki A, Echtay A, al-Zaben GS, Daher HS, Irani-Hakime NA, et al. Transcription factor-7-like 2 gene variants are strongly associated with type 2 diabetes in Lebanese subjects. Diabetes Res Clin Pract. 2012;98(3):e23–7.CrossRefPubMed
23.
Zurück zum Zitat Danquah I, et al. The TCF7L2 rs7903146 (T) allele is associated with type 2 diabetes in urban Ghana: a hospital-based case–control study. BMC Med Genet. 2013;14(1):1.CrossRef Danquah I, et al. The TCF7L2 rs7903146 (T) allele is associated with type 2 diabetes in urban Ghana: a hospital-based case–control study. BMC Med Genet. 2013;14(1):1.CrossRef
24.
Zurück zum Zitat Shokouhi S, Delpisheh A, Haghani K, Mahdizadeh M, Bakhtiyari S. Association of rs7903146, rs12255372, and rs290487 polymorphisms in TCF7L2 gene with type 2 diabetes in an Iranian Kurdish ethnic group. Clin Lab. 2014;60. Shokouhi S, Delpisheh A, Haghani K, Mahdizadeh M, Bakhtiyari S. Association of rs7903146, rs12255372, and rs290487 polymorphisms in TCF7L2 gene with type 2 diabetes in an Iranian Kurdish ethnic group. Clin Lab. 2014;60.
25.
26.
Zurück zum Zitat Wang J, et al. Meta-analysis of associations between TCF7L2 polymorphisms and risk of type 2 diabetes mellitus in the Chinese population. BMC Med Genet. 2013;14(1):1. Wang J, et al. Meta-analysis of associations between TCF7L2 polymorphisms and risk of type 2 diabetes mellitus in the Chinese population. BMC Med Genet. 2013;14(1):1.
27.
Zurück zum Zitat Bodhini D, Radha V, Dhar M, Narayani N, Mohan V. The rs12255372 (G/T) and rs7903146 (C/T) polymorphisms of the TCF7L2 gene are associated with type 2 diabetes mellitus in Asian Indians. Metabolism. 2007;56(9):1174–8.CrossRefPubMed Bodhini D, Radha V, Dhar M, Narayani N, Mohan V. The rs12255372 (G/T) and rs7903146 (C/T) polymorphisms of the TCF7L2 gene are associated with type 2 diabetes mellitus in Asian Indians. Metabolism. 2007;56(9):1174–8.CrossRefPubMed
28.
Zurück zum Zitat Miyake K, Horikawa Y, Hara K, Yasuda K, Osawa H, Furuta H, et al. Association of TCF7L2 polymorphisms with susceptibility to type 2 diabetes in 4,087 Japanese subjects. J Hum Genet. 2008;53(2):174–80.CrossRefPubMed Miyake K, Horikawa Y, Hara K, Yasuda K, Osawa H, Furuta H, et al. Association of TCF7L2 polymorphisms with susceptibility to type 2 diabetes in 4,087 Japanese subjects. J Hum Genet. 2008;53(2):174–80.CrossRefPubMed
29.
Zurück zum Zitat Cruz M, Valladares-Salgado A, Garcia-Mena J, Ross K, Edwards M, Angeles-Martinez J, et al. Candidate gene association study conditioning on individual ancestry in patients with type 2 diabetes and metabolic syndrome from Mexico City. Diabetes Metab Res Rev. 2010;26(4):261–70.CrossRefPubMed Cruz M, Valladares-Salgado A, Garcia-Mena J, Ross K, Edwards M, Angeles-Martinez J, et al. Candidate gene association study conditioning on individual ancestry in patients with type 2 diabetes and metabolic syndrome from Mexico City. Diabetes Metab Res Rev. 2010;26(4):261–70.CrossRefPubMed
30.
Zurück zum Zitat Sale MM, Smith SG, Mychaleckyj JC, Keene KL, Langefeld CD, Leak TS, et al. Variants of the transcription factor 7-like 2 (TCF7L2) gene are associated with type 2 diabetes in an African-American population enriched for nephropathy. Diabetes. 2007;56(10):2638–42.CrossRefPubMed Sale MM, Smith SG, Mychaleckyj JC, Keene KL, Langefeld CD, Leak TS, et al. Variants of the transcription factor 7-like 2 (TCF7L2) gene are associated with type 2 diabetes in an African-American population enriched for nephropathy. Diabetes. 2007;56(10):2638–42.CrossRefPubMed
31.
Zurück zum Zitat Wang J, Kuusisto J, Vänttinen M, Kuulasmaa T, Lindström J, Tuomilehto J, et al. Variants of transcription factor 7-like 2 (TCF7L2) gene predict conversion to type 2 diabetes in the Finnish Diabetes Prevention Study and are associated with impaired glucose regulation and impaired insulin secretion. Diabetologia. 2007;50(6):1192–200.CrossRefPubMed Wang J, Kuusisto J, Vänttinen M, Kuulasmaa T, Lindström J, Tuomilehto J, et al. Variants of transcription factor 7-like 2 (TCF7L2) gene predict conversion to type 2 diabetes in the Finnish Diabetes Prevention Study and are associated with impaired glucose regulation and impaired insulin secretion. Diabetologia. 2007;50(6):1192–200.CrossRefPubMed
Metadaten
Titel
Genome-wide implicated risk variants of TCF7L2 gene contribute to type 2 diabetes susceptibility by modulating serum lipids in Pakistani population
verfasst von
Shafiqa Shahzadi
Shabana
Sumbal Sarwar
Saleem Ullah Shahid
Publikationsdatum
21.09.2018
Verlag
Springer India
Erschienen in
International Journal of Diabetes in Developing Countries / Ausgabe 2/2019
Print ISSN: 0973-3930
Elektronische ISSN: 1998-3832
DOI
https://doi.org/10.1007/s13410-018-0694-2

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