Skip to main content
SpringerLink
Log in

A MCP-1 promoter polymorphism at G-2518A is associated with spontaneous preterm birth

  • Original Paper
  • Published:
Molecular Genetics and Genomics Aims and scope Submit manuscript

Abstract

Monocyte chemoattractant protein-1 (MCP-1) is an important chemokine involved in the pathogenesis of spontaneous preterm birth (SPTB). We examined whether the MCP-1 G-2518A polymorphism is associated with the risk of SPTB in a Chinese population. The MCP-1 G-2518A polymorphism was genotyped in 569 preterm singleton neonates and in 673 term neonates using polymerase chain reaction–restriction fragment length polymorphism analysis. The distribution of the MCP-1 G-2518A genotype and the allele frequencies between the SPTB patients and the controls were not significantly different in the overall sample. However, we found that the AA genotype was associated with significantly increased susceptibility to very SPTB (<32 weeks) [odds ratio (OR) 2.07; 95 % confidence interval (CI), 1.27–3.36; P = 0.005) and extremely SPTB (<28 weeks) (OR 2.74; 95 % CI, 1.10–6.72; P = 0.014) compared with −2518G-positive genotypes (GG + GA genotypes). When extremely preterm neonates and very preterm neonates were combined, the AA genotype was also significantly associated with increased susceptibility to SPTB (OR 2.23; 95 % CI, 1.40–3.54; P < 0.001). The MCP-1 G-2518A polymorphism was not associated with increased susceptibility to SPTB in patients with premature rupture of the membranes (PROM) or in those without PROM. Our findings suggest that the MCP-1 G-2518A polymorphism may plays a role in mediating the susceptibility to SPTB in the Chinese population. Knowledge of genetic factors contributing to the pathogenesis of SPTB may have implications for screening and treatment of this disorder.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Ahern J, Pickett KE, Selvin S, Abrams B (2003) Preterm birth among African American and white women: a multilevel analysis of socioeconomic characteristics and cigarette smoking. J Epidemiol Community Health 57:606–611

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Arji N, Busson M, Iraqi G, Bourkadi JE, Benjouad A, Boukouaci W, Lahlou O, Ben Amor J, Krishnamoorthy R, Charron D, El Aouad R, Tamouza R (2012) The MCP-1 (CCL2) -2518 GG genotype is associated with protection against pulmonary tuberculosis in Moroccan patients. J Infect Dev Ctries 6:73–78

    CAS  PubMed  Google Scholar 

  • Bardou M, Hadi T, Mace G, Pesant M, Debermont J, Barrichon M, Wendremaire M, Laurent N, Sagot P, Lirussi F (2014) Systemic increase in human maternal circulating CD14+CD16- MCP-1+monocytes as a marker of labor. Am J Obstet Gynecol 210(70):e71–e79

    Google Scholar 

  • Ben-Selma W, Harizi H, Boukadida J (2011) MCP-1 -2518 A/G functional polymorphism is associated with increased susceptibility to active pulmonary tuberculosis in Tunisian patients. Mol Biol Rep 38:5413–5419

    Article  CAS  PubMed  Google Scholar 

  • Bucova M, Lietava J, Mrazek F, Petrkova J, Penz P, Bernadic M, Buckingham TA, Petrek M (2009) The MCP-1 -2518 (A/G) single nucleotide polymorphism is associated with ischemic heart disease and myocardial infarction in men in the Slovak population. Bratisl Lek Listy 110:385–389

    CAS  PubMed  Google Scholar 

  • Chandiramani M, Seed PT, Orsi NM, Ekbote UV, Bennett PR, Shennan AH, Tribe RM (2012) Limited relationship between cervico-vaginal fluid cytokine profiles and cervical shortening in women at high risk of spontaneous preterm birth. PLoS One 7:e52412

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Dammann O, Phillips TM, Allred EN, O’Shea TM, Paneth N, Van Marter LJ, Bose C, Ehrenkranz RA, Bednarek FJ, Naples M, Leviton A (2001) Mediators of fetal inflammation in extremely low gestational age newborns. Cytokine 13:234–239

    Article  CAS  PubMed  Google Scholar 

  • Diamond AK, Sweet LM, Oppenheimer KH, Bradley DF, Phillippe M (2007) Modulation of monocyte chemotactic protein-1 expression during lipopolysaccharide-induced preterm delivery in the pregnant mouse. Reprod Sci 14:548–559

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Esplin MS, Peltier MR, Hamblin S, Smith S, Fausett MB, Dildy GA, Branch DW, Silver RM, Adashi EY (2005a) Monocyte chemotactic protein-1 expression is increased in human gestational tissues during term and preterm labor. Placenta 26:661–671

    Article  CAS  PubMed  Google Scholar 

  • Esplin MS, Romero R, Chaiworapongsa T, Kim YM, Edwin S, Gomez R, Mazor M, Adashi EY (2005b) Monocyte chemotactic protein-1 is increased in the amniotic fluid of women who deliver preterm in the presence or absence of intra-amniotic infection. J Matern Fetal Neonatal Med 17:365–373

    Article  CAS  PubMed  Google Scholar 

  • Kempe A, Wise PH, Barkan SE, Sappenfield WM, Sachs B, Gortmaker SL, Sobol AM, First LR, Pursley D, Rinehart H et al (1992) Clinical determinants of the racial disparity in very low birth weight. N Engl J Med 327:969–973

    Article  CAS  PubMed  Google Scholar 

  • Kim HL, Lee DS, Yang SH, Lim CS, Chung JH, Kim S, Lee JS, Kim YS (2002) The polymorphism of monocyte chemoattractant protein-1 is associated with the renal disease of SLE. Am J Kidney Dis 40:1146–1152

    Article  CAS  PubMed  Google Scholar 

  • Krediet TG, Wiertsema SP, Vossers MJ, Hoeks SB, Fleer A, Ruven HJ, Rijkers GT (2007) Toll-like receptor 2 polymorphism is associated with preterm birth. Pediatr Res 62:474–476

    Article  CAS  PubMed  Google Scholar 

  • Malafronte P, Vieira JM Jr, Pereira AC, Krieger JE, Barros RT, Woronik V (2010) Association of the MCP-1 -2518 A/G polymorphism and no association of its receptor CCR2 -64 V/I polymorphism with lupus nephritis. J Rheumatol 37:776–782

    Article  CAS  PubMed  Google Scholar 

  • Mashima Y, Konta T, Kudo K, Suzuki K, Ikeda A, Ichikawa K, Shibata Y, Watanabe T, Tamiya G, Kato T, Kawata S, Kubota I (2011) Polymorphism of proinflammatory cytokine genes and albuminuria in the Japanese general population: the Takahata study. Nephrol Dial Transplant 26:3902–3907

    Article  CAS  PubMed  Google Scholar 

  • Matoba N, Yu Y, Mestan K, Pearson C, Ortiz K, Porta N, Thorsen P, Skogstrand K, Hougaard DM, Zuckerman B, Wang X (2009) Differential patterns of 27 cord blood immune biomarkers across gestational age. Pediatrics 123:1320–1328

    Article  PubMed  Google Scholar 

  • Muglia LJ, Katz M (2010) The enigma of spontaneous preterm birth. N Engl J Med 362:529–535

    Article  CAS  PubMed  Google Scholar 

  • Murtha AP, Nieves A, Hauser ER, Swamy GK, Yonish BA, Sinclair TR, Heine RP (2006) Association of maternal IL-1 receptor antagonist intron 2 gene polymorphism and preterm birth. Am J Obstet Gynecol 195:1249–1253

    Article  CAS  PubMed  Google Scholar 

  • Nahon P, Sutton A, Rufat P, Faisant C, Simon C, Barget N, Trinchet JC, Beaugrand M, Gattegno L, Charnaux N (2007) Lack of association of some chemokine system polymorphisms with the risks of death and hepatocellular carcinoma occurrence in patients with alcoholic cirrhosis: a prospective study. Eur J Gastroenterol Hepatol 19:425–431

    Article  CAS  PubMed  Google Scholar 

  • Nahon P, Sutton A, Rufat P, Simon C, Trinchet JC, Gattegno L, Beaugrand M, Charnaux N (2008) Chemokine system polymorphisms, survival and hepatocellular carcinoma occurrence in patients with hepatitis C virus-related cirrhosis. World J Gastroenterol 14:713–719

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Nuk M, Orendi K, Rosenberger S, Griesbacher A, Holzapfel-Bauer M, Resch B, Lang U, Pertl B (2012) Genetic variations in fetal and maternal tumor necrosis factor-alpha and interleukin 10: is there an association with preterm birth or periventricular leucomalacia? J Perinatol 32:27–32

    Article  CAS  PubMed  Google Scholar 

  • Rey G, Skowronek F, Alciaturi J, Alonso J, Bertoni B, Sapiro R (2008) Toll receptor 4 Asp299Gly polymorphism and its association with preterm birth and premature rupture of membranes in a South American population. Mol Hum Reprod 14:555–559

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Rovin BH, Lu L, Saxena R (1999) A novel polymorphism in the MCP-1 gene regulatory region that influences MCP-1 expression. Biochem Biophys Res Commun 259:344–348

    Article  CAS  PubMed  Google Scholar 

  • Saenz-Lopez P, Carretero R, Cozar JM, Romero JM, Canton J, Vilchez JR, Tallada M, Garrido F, Ruiz-Cabello F (2008) Genetic polymorphisms of RANTES, IL1-A, MCP-1 and TNF-A genes in patients with prostate cancer. BMC Cancer 8:382

    Article  PubMed Central  PubMed  Google Scholar 

  • Sanders SK, Crean SM, Boxer PA, Kellner D, LaRosa GJ, Hunt SW 3rd (2000) Functional differences between monocyte chemotactic protein-1 receptor A and monocyte chemotactic protein-1 receptor B expressed in a Jurkat T cell. J Immunol 165:4877–4883

    Article  CAS  PubMed  Google Scholar 

  • Simeoni E, Hoffmann MM, Winkelmann BR, Ruiz J, Fleury S, Boehm BO, Marz W, Vassalli G (2004) Association between the A-2518G polymorphism in the monocyte chemoattractant protein-1 gene and insulin resistance and Type 2 diabetes mellitus. Diabetologia 47:1574–1580

    Article  CAS  PubMed  Google Scholar 

  • Sullivan SE, Staba SL, Gersting JA, Hutson AD, Theriaque D, Christensen RD, Calhoun DA (2002) Circulating concentrations of chemokines in cord blood, neonates, and adults. Pediatr Res 51:653–657

    Article  CAS  PubMed  Google Scholar 

  • Szalai C, Kozma GT, Nagy A, Bojszko A, Krikovszky D, Szabo T, Falus A (2001) Polymorphism in the gene regulatory region of MCP-1 is associated with asthma susceptibility and severity. J Allergy Clin Immunol 108:375–381

    Article  CAS  PubMed  Google Scholar 

  • Vazquez-Lavista LG, Lima G, Gabilondo F, Llorente L (2009) Genetic association of monocyte chemoattractant protein 1 (MCP-1)-2518 polymorphism in Mexican patients with transitional cell carcinoma of the bladder. Urology 74:414–418

    Article  PubMed  Google Scholar 

  • Wang Y, Yang X, Zheng Y, Wu ZH, Zhang XA, Li QP, He XY, Wang CZ, Feng ZC (2013) The SEPS1 G-105A polymorphism is associated with risk of spontaneous preterm birth in a Chinese population. PLoS One 8:e65657

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Yamauchi T, Houkin K, Tada M, Abe H (1997) Familial occurrence of moyamoya disease. Clin Neurol Neurosurg 99(Suppl 2):S162–S167

    Article  PubMed  Google Scholar 

  • Yang L, Shi GL, Song CX, Xu SF (2010) Relationship between genetic polymorphism of MCP-1 and non-small-cell lung cancer in the Han nationality of North China. Genet Mol Res 9:765–771

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We would like to thank all of the study participants, their families, and the collaborating clinicians for their participation. This work was supported by the National Natural Science Foundation of China (30973210, 81170602 and 81300527).

Conflict of interest

The authors declare no conflict of interest.

Author information

Authors and Affiliations

  1. BaYi Children’s Hospital, General Military Hospital of Beijing PLA, 5 Nanmencang Road, Dongcheng District, Beijing, 100700, People’s Republic of China

    Yan Wang, Xiao Yang & Zhi-Chun Feng

  2. State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, 100071, People’s Republic of China

    Xiao-Ai Zhang

  3. Department of Infectious Disease Control, Beijing Institute of Disease Control and Prevention, 20 Dong Da Jie Street, Fengtai District, Beijing, 100071, People’s Republic of China

    Zhi-Hao Wu

  4. Clinical Medical College, Second Military Medical University, Shanghai, 200433, People’s Republic of China

    Xiao Yang

Authors
  1. Yan Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xiao-Ai Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xiao Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Zhi-Hao Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Zhi-Chun Feng
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Zhi-Hao Wu or Zhi-Chun Feng.

Additional information

Communicated by S. Hohmann.

Y. Wang, X.-A. Zhang and X. Yang contributed equally to the paper.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, Y., Zhang, XA., Yang, X. et al. A MCP-1 promoter polymorphism at G-2518A is associated with spontaneous preterm birth. Mol Genet Genomics 290, 289–296 (2015). https://doi.org/10.1007/s00438-014-0921-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00438-014-0921-6

Keywords

Search

Navigation