Glucokinase gene promoter -30G>A polymorphism: a cross-sectional association study with obesity, diabetes Mellitus, hyperlipidemia, hypertension and metabolic syndrome in an Iranian hospital

Authors

  • Mohammad Reza OLADI Mashhad University of Medical Sciences
  • Javad BEHRAVAN Mashhad University of Medical Sciences
  • Mitra HASSANI Mashhad University of Medical Sciences
  • Jamal KASSAEIAN Mashhad University of Medical Sciences
  • Amirhossein SAHEBKAR Mashhad University of Medical Sciences
  • Shima TAVALLAIE Mashhad University of Medical Sciences
  • Roghayeh PAYDAR Mashhad University of Medical Sciences
  • Hamidreza SABER Mashhad University of Medical Sciences
  • Habib Allah ESMAEILI Mashhad University of Medical Sciences
  • Mohsen AZIMI-NEZHAD Mashhad University of Medical Sciences
  • Gordon FERNS University of Keele
  • Majid GHAYOUR-MOBARHAN Mashhad University of Medical Sciences

Keywords:

Body mass index, Glucokinase, Metabolic syndrome, Obesity, Single nucleotide polymorphism

Abstract

Objective
A -30G>A single nucleotide polymorphism in the promoter region of the glucokinase gene has been previously associated with obesity, insulin resistance and diabetes. The present study aimed to evaluate the association of this polymorphism with obesity and its comorbidities in a population from Northeast Iran.

Methods
Five hundred and forty-two subjects aged 18 to 65 years were included in the study and divided into normal (BMI<25, n=220), overweight (25<BMI<30, n=135) and obese (BMI>30, n=187) groups. All subjects were genotyped for the -30G>A polymorphism using the polymerase chain reaction-restriction fragment length polymorphism technique.

Results
The genotypes and allele frequencies of the three groups did not differ significantly (p>0.05). When the study population was categorized according to diabetes mellitus, hyperlipidemia, hypertension and metabolic syndrome status, no significant difference in -30G>A genotypes and alleles was found between the subgroups with and without these disorders (p>0.05), apart from a significantly higher frequency of the G allele in the hyperlipidemic vs. non-hyperlipidemic subgroup (p<0.05).

Conclusion
The findings of the present study do not support an association between the -30G>A polymorphism and high body mass index in the Iranian population.

References

Sobal J, Stunkard AJ. Socioeconomic status and obesity: a review of the literature. Psychol Bull. 1989; 105(2):260-75.

Lau DC, Douketis JD, Morrison KM, Hramiak IM, Sharma AM, Ur E. Obesity Canada clinical practice guidelines expert panel. 2006 Canadian clinical practice guidelines on the management and prevention of obesity in adults and children [summary]. CMAJ. 2007; 176(8):S1-13.

Comuzzie AG, Allison DB. The search for human obesity genes. Science. 1998; 280(5386):1374-7.

Rankinen T, Pérusse L, Weisnagel SJ, Snyder EE, Chagnon YC, Bouchard C. The human obesity gene map: the 2001 update. Obes Res. 2002; 10(3): 196-243.

Luis DA, Perez Castrillón JL, Dueñas A. Leptin and obesity. Minerva Med. 2009; 100(3):229-36.

Kawano J, Arora R. The role of adiponectin in obesity, diabetes, and cardiovascular disease. J Cardiometab Syndrome. 2009; 4(1):44-9.

Matschinsky F, Liang Y, Kesavan P, Wang L, Froguel P, Velho G, et al. Glucokinase as pancreatic beta cell glucose sensor and diabetes gene. J Clin Invest. 1993; 92(5):2092-8.

Zelent D, Golson ML, Koeberlein B, Quintens R, van Lommel L, Buettger C, et al. A glucose sensor role for glucokinase in anterior pituitary cells. Diabetes. 2006; 55(7):1923-9.

Yang X, Mastaitis J, Mizuno T, Mobbs CV. Glucokinase regulates reproductive function, glucocorticoid secretion, food intake, and hypothalamic gene expression. Endocrinology. 2007; 148(4):1928-32.

Gómez-Zumaquero JM, Rojo-Martínez G, GarcíaEscobar E, Martín-Nuñez GM, Haro J, Esteva I, et al. The -30G>A polymorphism of the glucokinase gene promoter is associated with obesity in a population from Southern Spain. Obesity. 2008; 16(8):1973-5.

Froguel P, Vaxillaire M, Sun F, Velho G, Zouali H, Butel MO, et al. Close linkage of glucokinase locus on chromosome 7p to early-onset non-insulindependent diabetes Mellitus. Nature. 1992; 356(6365):162-4.

Yamada K, Yuan X, Ishiyama S, Ichikawa F, Koyama KI, Koyanagi A, et al. Clinical characteristics of Japanese men with glucokinase gene E-cell promoter variant. Diabetes Care. 1997; 20(7): 1159-61.

März W, Nauck M, Hoffmann MM, Nagel D, Boehm BO, Koenig W, et al. G(-30)A polymorphism in the pancreatic promoter of the glucokinase gene associated with angiographic coronary artery disease and type 2 diabetes Mellitus. Circulation. 2004; 109(23):2844-9.

Chiu KC, Chuang LM, Yoon C, Saad MF. Hepatic glucokinase promoter polymorphism is associated with hepatic insulin resistance in Asian Indians. BMC Genet. 2000; 1:2.

Rose CS, Ek J, Urhammer SA, Glumer C, BorchJohnsen K, Jorgensen T, et al. A -30G>A polymorphism of the beta-cell-specific glucokinase promoter associates with hyperglycemia in the general population of whites. Diabetes. 2005; 54(10):3026-31.

Price CP, Trull AK, Berry D, Gorman EG. Development and validation of a particle-enhanced turbidimetric immunoassay for C-reactive protein. J Immunol Methods. 1987; 99(2):205-11.

Eda S, Kaufmann J, Roos W, Pohl S. Development of a new microparticle-enhanced turbidimetric immunoassay for C-reactive protein with superior features in sensitivity and dynamic range. J Clin Lab Anal. 1998; 12(3):137-44.

Tatari F, Salek R, Mosaffa F, Behravan J. Association of C3435T single nucleotide polymorphism of MDR1 gene with breast cancer in an Iranian population. DNA Cell Biol. 2009; 28(5):259-63.

Yamada Y, Kato K, Kameyama T, Yokoi K, Matsuo H, Segawa T, et al. Genetic factors for obesity. Int J Mol Med. 2006; 18(5):843-51.

Elbein SC, Sun J, Scroggin E, Teng K, Hasstedt SJ. Role of common sequence variants in insulin secretion in familial type 2 diabetic kindreds: the sulfonylurea receptor, glucokinase, and hepatocyte nuclear factor 1alpha genes. Diabetes Care. 2001; 24(3):472-8.

Weedon MN, Frayling TM, Shields B, Knight B, Turner T, Metcalf BS, et al. Genetic regulation of birth weight and fasting glucose by a common polymorphism in the islet cell promoter of the glucokinase gene. Diabetes. 2005; 54(2):576-81.

Tam CH, Ma RC, So WY, Wang Y, Lam VK, Germer S, et al. Interaction effect of genetic polymorphisms in glucokinase (GCK) and glucokinase regulatory protein (GCKR) on metabolic traits in healthy Chinese adults and adolescents. Diabetes. 2009; 58(3):765-9.

Lotfi K, Sund G, Lowe R, Graham J, Landin-Olsson M, Kockum I, et al. The beta cell glucokinase promoter variant is an unlikely risk factor for diabetes mellitus: Diabetes Incidence Study in Sweden (DISS). Diabetologia. 1997; 40(8):959-62.

Rissanen J, Saarinen L, Heikkinen S, Kekalainen P, Mykkanen L, Kuusisto J, et al. Glucokinase gene islet promoter region variant (G3A) at nucleotide30 is not associated with reduced insulin secretion in Finns. Diabetes Care. 1998; 21(7):1194-7.

Shimokawa K, Sakura H, Otabe S, Eto K, Kadowaki H, Hagura R, et al. Analysis of the glucokinase gene promoter in Japanese subjects with noninsulindependent diabetes mellitus. J Clin Endocrinol Metab. 1994; 79(3):883-6.

Ezzidi I, Mtiraoui N, Cauchi S, Vaillant E, Dechaume A, Chaieb M, et al. Contribution of type 2 diabetes associated loci in the arabic population from tunisia: a case-control study. BMC Med Genet. 2009; 10: 33.

Stone LM, Kahn SE, Fujimoto WY, Deeb SS, Porte D Jr. A variation at position -30 of the beta-cell glucokinase gene promoter is associated with reduced beta-cell function in middle-aged Japanese-American men. Diabetes. 1996; 45(4): 422-8.

Qi Q, Wu Y, Li H, Loos RJF, Hu FB, Sun L, et al. Association of GCKR rs780094, alone or in combination with GCK rs1799884, with type 2 diabetes and related traits in a han Chinese population. Diabetologia. 2009; 52(5):834-43.

Matsutani A, Noda K, Tao T, Tanizawa Y, Kaneko T, Kaku K, et al. Variation of promoter activity of glucokinase gene in humans. Diabetes. 1993; 42:94A.

Zaidi FK, Wareham NJ, McCarthy MI, Holdstock J, Kalloo-Hosein H, Krook A, et al. Homozygosity for a common polymorphism in the islet-specific promoter of the glucokinase gene is associated with a reduced early insulin response to oral glucose in pregnant women. Diabet Med. 1997; 14(3): 228-34.

Urhammer SA, Hansen T, Clausen JO, Eiberg H, Pedersen O. The G/A nucleotide variant at position -30 in the beta-cell-specific glucokinase gene promoter has no impact on the beta-cell function in Danish Caucasians. Diabetes. 1998; 47(8): 1359-61.

Li X, Shu YH, Xiang AH, Trigo E, Kuusisto J, Hartiala J, et al. Additive effects of genetic variation in GCK and G6PC2 on insulin secretion and fasting glucose. Diabetes. 2009; 58(12):2946-53.

Lewis GF, Uffelman KD, Szeto LW, Weller B, Steiner G. Interaction between free fatty acids and insulin in the acute control of very low density lipoprotein production in humans. J Clin Invest. 1995; 95(1): 158-66.

Taskinen MR. Insulin resistance and lipoprotein metabolism. Curr Opin Lipodol. 1995; 6(3): 153-60.

Yamada Y, Matsuo H, Segawa T, Watanabe S, Kato K, Hibino T, et al. Assessment of the genetic component of hypertension. Am J Hypertens. 2006; 19(11):1158-65.

Yamada Y, Ando F, Shimokata H. Association of polymorphisms of SORBS1, GCK and WISP1 with hypertension in community-dwelling Japanese individuals. Hypertens Res. 2009; 32(5):325-31.

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Published

2023-08-22

How to Cite

Reza OLADI, M. ., BEHRAVAN, J., HASSANI, M. ., KASSAEIAN, J. ., SAHEBKAR, A. ., TAVALLAIE, S. ., … GHAYOUR-MOBARHAN, M. (2023). Glucokinase gene promoter -30G>A polymorphism: a cross-sectional association study with obesity, diabetes Mellitus, hyperlipidemia, hypertension and metabolic syndrome in an Iranian hospital. Brazilian Journal of Nutrition, 25(4). Retrieved from https://puccampinas.emnuvens.com.br/nutricao/article/view/9281

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ORIGINAL ARTICLE