Horm Metab Res 2017; 49(01): 10-15
DOI: 10.1055/s-0042-111436
Endocrine Care
© Georg Thieme Verlag KG Stuttgart · New York

CCL2, CCL5, IL4 and IL15 Gene Polymorphisms in Women with Gestational Diabetes Mellitus

Joanna Teler
1   Department of Obstetrics and Gynecology, County Hospital, Zielona Góra, Poland
,
Maciej Tarnowski
2   Department of Physiology, Pomeranian Medical University, Szczecin, Poland
,
Krzysztof Safranow
3   Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, Szczecin, Poland
,
Agnieszka Maciejewska
4   Faculty of Physical Education and Health Promotion, University of Szczecin, Szczecin, Poland
,
Marek Sawczuk
4   Faculty of Physical Education and Health Promotion, University of Szczecin, Szczecin, Poland
,
Violetta Dziedziejko
3   Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, Szczecin, Poland
,
Sylwia Sluczanowska-Glabowska
2   Department of Physiology, Pomeranian Medical University, Szczecin, Poland
,
Andrzej Pawlik
2   Department of Physiology, Pomeranian Medical University, Szczecin, Poland
› Author Affiliations
Further Information

Publication History

received 04 April 2016

accepted 23 June 2016

Publication Date:
29 July 2016 (online)

Abstract

Gestational diabetes mellitus (GDM) is a glucose intolerance that occurs during pregnancy. Several studies suggest that inflammation contributes to pregnancy-induced insulin resistance and the development of glucose intolerance. The aim of this study is to examine the association between the CCL2, CCL5, IL4 and IL15 gene polymorphisms and the development of GDM. This study included 411 pregnant women who underwent a 75 g oral glucose tolerance test at 24–28 weeks of gestation. Participants were categorised into 2 groups according to results of the oral glucose tolerance test (OGTT). The GDM group included 204 pregnant women who were diagnosed with GDM. The normal glucose tolerance group included 207 pregnant women with normal values in the OGTT. To discriminate the CCL2 rs1024611 and rs4586, CCL5 rs2107538, IL4 rs2243250, IL15 rs2857261 and rs2254514 alleles, TaqMan® Pre-Designed SNP Genotyping Assays were used. GDM was significantly associated with genotypes and alleles of the CCL2 rs1024611 and rs4586 polymorphisms, while there was no statistically significant association between the CCL5 rs2107538, IL4 rs2243250, IL15 rs2857261, and rs2254514 gene polymorphisms and GDM. In a multivariate regression analysis, age and BMI before pregnancy were independent significant predictors of a higher risk of GDM, while a lower number of G alleles CCL2 rs1024611 was protective against GDM. Moreover, women with the GG CCL2 rs1024611 and CC rs4586 genotype tended to have lower body mass and BMI increases during pregnancy, as well as lower newborn body mass. The results of our study suggest an association between CCL2 gene polymorphisms and GDM.

Supporting Information

 
  • References

  • 1 Sullivan SD, Umans JG, Ratner R. Gestational diabetes: implications for cardiovascular health. Curr Diab Rep 2012; 12: 43-52
  • 2 Verma A, Boney CM, Tucker R, Vohr BR. Insulin resistance syndrome in women with prior history of gestational diabetes mellitus. J Clin Endocrinol Metab 2002; 87: 3227-3235
  • 3 Heitritter SM, Solomon CG, Mitchell GF, Skali-Ounis N, Seely EW. Subclinical inflammation and vascular dysfunction in women with previous gestational diabetes mellitus. J Clin Endocrinol Metab 2005; 90: 3983-3988
  • 4 Rossi D, Zlotnik A. The biology of chemokines and their receptors. Annu Rev Immunol 2000; 18: 217-242
  • 5 Richardson AC, Carpenter MW. Inflammatory mediators in gestational diabetes mellitus. Obstet Gynecol Clin North Am 2007; 34: 213-224
  • 6 Jamali Z, Nazari M, Khoramdelazad H, Hakimizadeh E, Mahmoodi M, Karimabad MN, Hassanshahi G, Rezaeian M, Balaei P, Darakhshan S, Poor NM. Expression of CC chemokines CCL2, CCL5, and CCL11 is associated with duration of disease and complications in type-1 diabetes: a study on Iranian diabetic patients. Clin Lab 2013; 59: 993-1001
  • 7 Mirhafez SR, Pasdar A, Avan A, Esmaily H, Moezzi A, Mohebati M, Meshkat Z, Mehrad-Majd H, Eslami S, Rahimi HR, Ghazavi H, Ferns GA, Ghayour-Mobarhan M. Cytokine and growth factor profiling in patients with the metabolic syndrome. Br J Nutr 2015; 113: 1911-1919
  • 8 Schmidt FM, Weschenfelder J, Sander C, Minkwitz J, Thormann J, Chittka T, Mergl R, Kirkby KC, Faßhauer M, Stumvoll M, Holdt LM, Teupser D, Hegerl U, Himmerich H. Inflammatory cytokines in general and central obesity and modulating effects of physical activity. PLoS One 2015; 10: e0121971
  • 9 Nehete P, Magden ER, Nehete B, Hanley PW, Abee CR. Obesity related alterations in plasma cytokines and metabolic hormones in chimpanzees. Int J Inflam 2014; 2014: 856749
  • 10 Nielsen AR, Hojman P, Erikstrup C, Fischer CP, Plomgaard P, Mounier R, Mortensen OH, Broholm C, Taudorf S, Krogh-Madsen R, Lindegaard B, Petersen AM, Gehl J, Pedersen BK. Association between interleukin-15 and obesity: interleukin-15 as a potential regulator of fat mass. J Clin Endocrinol Metab 2008; 93: 4486-4493
  • 11 Kuczyński S, Winiarska H, Abramczyk M, Szczawińska K, Wierusz-Wysocka B, Dworacka M. IL-15 is elevated in serum patients with type 1 diabetes mellitus. Diabetes Res Clin Pract 2005; 69: 231-236
  • 12 Sánchez-Jiménez R, Alvarado-Vásquez N. IL-15 that a regulator of TNF-α in patients with diabetes mellitus type 2. Med Hypotheses 2013; 80: 776-777
  • 13 Chang YH, Ho KT, Lu SH, Huang CN, Shiau MY. Regulation of glucose/lipid metabolism and insulin sensitivity by interleukin-4. Int J Obes (Lond) 2012; 36: 993-998
  • 14 Flores-Villanueva PO, Ruiz-Morales JA, Song CH, Flores LM, Jo EK, Montaño M, Barnes PF, Selman M, Grandos J. A functional promoter polymorphism in monocyte chemoattractant protein-1 is associated with increased susceptibility to pulmonary tuberculosis. J Exp Med 2005; 202: 1649-1658
  • 15 Liu H, Chao D, Nakayama EE, Taguchi H, Goto M, Xin X, Takamatsu JK, Saito H, Ishikawa Y, Akaza T, Juji T, Takebe Y, Ohishi T, Fukutake K, Maruyama Y, Yashiki S, Sonoda S, Nakamura T, Nagai Y, Iwamoto A, Shioda T. Polymorphism in RANTES chemokine promoter affects HIV-1 disease progression. Proc Natl Acad Sci U S A 1999; 96: 4581-4585
  • 16 Song Z, Casolaro V, Chen R, Georas SN, Monos D, Ono SJ. Polymorphic nucleotides within the human IL-4 promoter that mediate overexpression of the gene. J Immunol 1996; 156: 424-429
  • 17 Shang H, Cao XL, Wan YJ, Meng J, Guo LH. IL-4 Gene Polymorphism May Contribute to an Increased Risk of Atopic Dermatitis in Children. Dis Markers 2016; 2016: 1021942
  • 18 Zhang X, Sun XH, Li M, Zhou ZH, Gao YQ. A promoter polymorphism (rs3806798) of interleukin-15 gene is associated with chronic hepatitis B virus infection in the Chinese Han population. Int J Immunogenet 2014; 41: 298-305
  • 19 Yamamoto-Furusho JK, De-León-Rendón JL, Alvarez-León E, Valdivia-Eziquio M, Obil-Chavarría C, Vargas-Alarcón G. Association of the interleukin 15 (IL-15) gene polymorphisms with the risk of developing ulcerative colitis in Mexican individuals. Mol Biol Rep 2014; 41: 2171-2176
  • 20 Ho KT, Shiau MY, Chang YH, Chen CM, Yang SC, Huang CN. Association of interleukin-4 promoter polymorphisms in Taiwanese patients with type 2 diabetes mellitus. Metabolism 2010; 59: 1717-1722
  • 21 Alsaid A, El-Missiry M, Hatata el-S, Tarabay M, Settin A. Association of IL-4-590 C>T and IL-13-1112 C>T gene polymorphisms with the susceptibility to type 2 diabetes mellitus. Dis Markers 2013; 35: 243-247
  • 22 Zouidi F, Stayoussef M, Bouzid D, Fourati H, Abida O, João C, Ayed MB, Fakhfakh R, Thouraya K, Monjia H, Carlos PG, Masmoudi H. Association of BANK1 and cytokine gene polymorphisms with type 1 diabetes in Tunisia. Gene 2014; 536: 296-301
  • 23 Kaur R, Matharoo K, Arora P, Bhanwer AJ. Association of –2518A>G Promoter Polymorphism in the Monocyte Chemoattractant Protein-1 (MCP-1) Gene with Type 2 Diabetes and Coronary Artery Disease. Genet Test Mol Biomarkers 2013; 17: 750-755
  • 24 Herder C, Illig T, Baumert J, Müller M, Klopp N, Khuseyinova N, Meisinger C, Poschen U, Martin S, Koenig W, Thorand B. RANTES/CCL5 gene polymorphisms, serum concentrations, and incident type 2 diabetes: results from the MONICA/KORA Augsburg case-cohort study, 1984-2002. Eur J Endocrinol 2008; 158: R1-R5
  • 25 International Association of Diabetes and Pregnancy Study Groups Consensus Panel . International association of diabetes and pregnancy study groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy. Diabetes Care 2010; 33: 676-682
  • 26 Simeoni E, Hoffmann MM, Winkelmann BR, Ruiz J, Fleury S, Boehm BO, März W, Vassalli G. Association between the A-2518 G polymorphism in the monocyte chemoattractant protein-1 gene and insulin resistance and Type 2 diabetes mellitus. Diabetologia 2004; 47: 1574-1580
  • 27 Zhang Y, Zhang J, Tian C, Narenqimuge Deng Y, Zhao Y, Fan H, Huang J. The -2518A/G polymorphism in the monocyte chemoattractant protein-1 (MCP-1) gene and diabetes risk: a meta-analysis. Diabetes Res Clin Pract 2011; 94: e89-e92
  • 28 Jing Y, Zhu D, Bi Y, Yang D, Hu Y, Shen S. Monocyte chemoattractant protein 1-2518A/G polymorphism and susceptibility to type 2 diabetes in a Chinese population. Clin Chim Acta 2011; 412: 466-469
  • 29 Karadeniz M, Erdogan M, Cetinkalp S, Berdeli A, Eroglu Z, Ozgen AG. Monocyte chemoattractant protein-1 (MCP-1) 2518G/A gene polymorphism in Turkish type 2 diabetes patients with nephropathy. Endocrine 2010; 37: 513-517
  • 30 Moon JY, Jeong L, Lee S, Jeong K, Lee T, Ihm CG, Suh J, Kim J, Jung YY, Chung JH. Association of polymorphisms in monocyte chemoattractant protein-1 promoter with diabetic kidney failure in Korean patients with type 2 diabetes mellitus. J Korean Med Sci 2007; 22: 810-814
  • 31 Daniele G, Guardado Mendoza R, Winnier D, Fiorentino TV, Pengou Z, Cornell J, Andreozzi F, Jenkinson C, Cersosimo E, Federici M, Tripathy D, Folli F. The inflammatory status score including IL-6, TNF-α, osteopontin, fractalkine, MCP-1 and adiponectin underlies whole-body insulin resistance and hyperglycemia in type 2 diabetes mellitus. Acta Diabetol 2014; 51: 123-131
  • 32 Kim CS, Park HS, Kawada T, Kim JH, Lim D, Hubbard NE, Kwon BS, Erickson KL, Yu R. Circulating levels of MCP-1 and IL-8 are elevated in human obese subjects and associated with obesity-related parameters. Int J Obes (Lond) 2006; 30: 1347-1355
  • 33 Gerhardt CC, Romero IA, Cancello R, Camoin L, Strosberg AD. Chemokines control fat accumulation and leptin secretion by cultured human adipocytes. Mol Cell Endocrinol 2001; 175: 81-92
  • 34 Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante Jr. AW. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 2003; 112: 1796-1808
  • 35 Westerbacka J, Cornér A, Kolak M, Makkonen J, Turpeinen U, Hamsten A, Fisher RM, Yki-Järvinen H. Insulin regulation of MCP-1 in human adipose tissue of obese and lean women. Am J Physiol Endocrinol Metab 2008; 294: e841-e845
  • 36 Younce CW, Azfer A, Kolattukudy PE. MCP-1 (monocyte chemotactic protein-1)-induced protein, a recently identified zinc finger protein, induces adipogenesis in 3T3-L1 pre-adipocytes without peroxisome proliferator-activated receptor gamma. J Biol Chem 2009; 284: 27620-27628
  • 37 Ota T. Chemokine systems link obesity to insulin resistance. Diabetes Metab J 2013; 37: 165-172
  • 38 Dworacka M, Krzyżagórska E, Iskakova S, Bekmukhambetov Y, Urazayev O, Dworacki G. Increased circulating RANTES in type 2 diabetes. Eur Cytokine Netw 2014; 25: 46-51
  • 39 Gnudi L. A new chance to beat diabetic kidney disease: innate immunity and MCP-1: a matter of good and bad macrophages?. Nephrol Dial Transplant 2015; 30: 525-527
  • 40 Briana DD, Boutsikou M, Baka S, Papadopoulos G, Gourgiotis D, Puchner KP, Hassiakos D, Malamitsi-Puchner A. Perinatal plasma monocyte chemotactic protein-1 concentrations in intrauterine growth restriction. Mediators Inflamm 2007; 2007: 65032
  • 41 Klein K, Satler M, Elhenicky M, Brix J, Krzyzanowska K, Schernthaner G, Husslein PW, Schernthaner GH. Circulating levels of MCP-1 are increased in women with gestational diabetes. Prenat Diagn 2008; 2: 845-851
  • 42 Wender-Ozegowska E, Michalowska-Wender G, Zawiejska A, Pietryga M, Brazert J, Wender M. Concentration of chemokines in peripheral blood in first trimester of diabetic pregnancy. Acta Obstet Gynecol Scand 2008; 87: 14-19
  • 43 Kurepa D, Pramanik AK, Kakkilaya V, Caldito G, Groome LJ, Bocchini JA, Jain SK. Elevated acetoacetate and monocyte chemotactic protein-1 levels in cord blood of infants of diabetic mothers. Neonatology 2012; 102: 163-168