Skip to main content

Advertisement

SpringerLink
Log in

Association between type 2 diabetes and rs10811661 polymorphism upstream of CDKN2A/B: a meta-analysis

  • Review Article
  • Published:
Acta Diabetologica Aims and scope Submit manuscript

Abstract

To assess the association between type 2 diabetes and rs10811661 polymorphism, upstream of CDKN2A/B, a literature-based search was conducted to collect data. The pooled OR (odds ratio) and 95 % confidence intervals (CI) were used to assess the strength of association between rs10811661 polymorphism and type 2 diabetes. OR with 95 % CI were performed for allele contrasts, additive genetic model, dominant genetic model and recessive genetic model, respectively. The effect model was used if there was heterogeneity between studies. Funnel plots were used to predict publication bias. 17 studies with 29,990 cases and 40,977 controls were enrolled in this meta-analysis. Significant association was found in all of the four genetic models: allele contrast (OR = 1.21, 95 % CI 1.18–1.24), additive genetic model (OR = 1.51, 95 % CI 1.40–1.63), dominant genetic model (OR = 1.37, 95 % CI 1.28–1.47) and recessive genetic model (OR = 1.25, 95 % CI 1.21–1.29). The meta-analysis indicated that rs10811661 polymorphism was significantly associated with the risk of type 2 diabetes.

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

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Khamaisi M, Raz I (2002) Diabetes epidemic and thrifty genes. Isr Med Assoc J 4(9):720–721

    PubMed  Google Scholar 

  2. Shaw JE, Sicree RA, Zimmet PZ (2010) Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract 87(1):4–14

    Article  PubMed  CAS  Google Scholar 

  3. Wild S, Roglic G, Green A, Sicree R, King H (2004) Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care 27(5):1047–1053

    Article  PubMed  Google Scholar 

  4. Voight BF, Scott LJ, Steinthorsdottir V et al (2010) Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis. Nat Genet 42(7):579–589

    Article  PubMed  CAS  Google Scholar 

  5. Trevers ME, McCarthy MI (2011) Type 2 diabetes and obesity: genomics and the clinic. Hum Genet 130(1):41–58

    Article  Google Scholar 

  6. Hribal ML, Presta I, Procopio T et al (2011) Glucose tolerance, insulin sensitivity and insulin release in European non-diabetic carriers of a polymorphism upstream of CDKN2A and CDKN2B. Diabetologia 54:795–802

    Article  PubMed  CAS  Google Scholar 

  7. Rane SG, Dubus P, Mettus RV et al (1999) Loss of Cdk4 expression causes insulin-deficient diabetes and Cdk4 activation results in beta-islet cell hyperplasia. Nat Genet 22(1):44–52

    Article  PubMed  CAS  Google Scholar 

  8. Moritani M, Yamasaki S, Kagami M et al (2005) Hypoplasia of endocrine and exocrine pancreas in homozygous transgenic TGF-beta-1. Mol Cell Endocrinol 229(1–2):175–184

    Article  PubMed  CAS  Google Scholar 

  9. Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analysis. BMJ 327(7414):557–560

    Article  PubMed  Google Scholar 

  10. Kim WY, Sharpless NE (2006) The regulation of INK4/ARF in cancer and aging. Cell 127(2):265–275

    Article  PubMed  CAS  Google Scholar 

  11. Cauchi S, Meyre D, Durand E et al (2008) Post genome-wide association studies of novel genes associated with type 2 diabetes show gene–gene interaction and high predictive value. PLoS One 3(5):e2031

    Article  PubMed  Google Scholar 

  12. Cauchi S, Proena C, Choquet H et al (2008) Analysis of novel risk loci for type 2 diabetes in a general French population: the D.E.S.I.R. study. J Mol Med 86(3):341–348

    Article  PubMed  CAS  Google Scholar 

  13. Duesing K, Fatemifar G, Charpentier G et al (2008) Strong association of common variants in the CDKN2A/CDKN2B region with type 2 diabetes in French Europids. Diabetologia 51(5):821–826

    Article  PubMed  CAS  Google Scholar 

  14. Grarup N, Rose CS, Andersson EA et al (2007) Studies of association of variants near the HHEX, CDKN2A/B, and IGF2BP2 genes with type 2 diabetes and impaired insulin release in 10,705 Danish subjects: validation and extension of genome-wide association studies. Diabetes 56(12):3105–3111

    Article  PubMed  CAS  Google Scholar 

  15. Groenewoud MJ, Dekker JM, Fritsche A et al (2008) Variants of CDKAL1 and IGF2BP2 affect first-phase insulin secretion during hyperglycaemic clamps. Diabetologia 51(9):1659–1663

    Article  PubMed  CAS  Google Scholar 

  16. Han X, Luo Y, Ren Q et al (2010) Implication variants near SLC30A8, HHEX, CDKAL1, CDKN2A/B, IGF2BP2, FTO, TCF2, KCNQ1, and WFS1 in type 2 diabetes in a Chinese population. BMC Med Genet 11:81

    Article  PubMed  Google Scholar 

  17. Horikoshi M, Hara K, Ito C et al (2007) Variations in the HHEX gene are associated with increased risk of type 2 diabetes in the Japanese population. Diabetologia 50(12):2461–2466

    Article  PubMed  CAS  Google Scholar 

  18. Kirchhoff K, Machicao F, Haupt A et al (2008) Polymorphisms in the TCF7L2, CDKAL1 and SLC30A8 genes are associated with impaired proinsulin conversion. Diabetologia 51(4):597–601

    Article  PubMed  CAS  Google Scholar 

  19. Lauenborg J, Grarup N, Damm P et al (2009) Common type 2 diabetes risk gene variants associate with gestational diabetes? J Clin Endocrinol Metab 94(1):145–150

    Article  PubMed  CAS  Google Scholar 

  20. Omori S, Tanaka Y, Takahashi A et al (2008) Association of CDKAL1, IGF2BP2, CDKN2A/B, HHEX, SLC30A8, and KCNJ11 with susceptibility to type 2 diabetes in a Japanese population. Diabetes 57(3):791–795

    Article  PubMed  CAS  Google Scholar 

  21. Sanghera DK, Ortega L, Han S et al (2008) 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

    Article  PubMed  Google Scholar 

  22. Saxena R, Voight BF, Lyssenko V et al (2007) Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels. Science 316(5829):1331–1336

    Article  PubMed  CAS  Google Scholar 

  23. Scott LJ, Mohlke KL, Bonnycastle LL et al (2007) A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants. Science 316(5829):1341–1345

    Article  PubMed  CAS  Google Scholar 

  24. Tabara Y, Osawa H, Kawamoto R et al (2009) Replication study of candidate genes associated with type 2 diabetes based on genome-wide screening. Diabetes 58(2):493–498

    Article  PubMed  CAS  Google Scholar 

  25. Wen J, Ronn T, Olsson A et al (2010) Investigation of type 2 diabetes risk alleles support CDKN2A/B, CDKAL1, and TCF7L2 as susceptibility genes in a Han Chinese cohort. PLoS One 5(2):e9153

    Article  PubMed  Google Scholar 

  26. Yukio H, Kazuaki M, Kazuki Y et al (2008) Replication of genome-wide association studies of type 2 diabetes susceptibility in Japan. Clin Endocrinol Metab 93(8):3136–3141

    Article  Google Scholar 

  27. Zeggini E, Weedon MN, Lindgren CM et al (2007) Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes. Science 316(5829):1336–1341

    Article  PubMed  CAS  Google Scholar 

  28. Parra EJ, Below JE, Krithika S et al (2011) Genome-wide association study of type 2 diabetes in a sample from Mexico City and a meta-analysis of a Mexican-American sample from Starr County, Texas. Diabetologia 54(8):2038–2046

    Article  PubMed  CAS  Google Scholar 

  29. Chidambaram M, Radha V, Mohan V (2010) Replication of recently described type 2 diabetes gene variants in a South Indian population. Metabolism 59(12):1760–1766

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. School of Public Health and Management, Chongqing Medical University, Chongqing, China

    Hui Li, Xiaojun Tang, Qin Liu & Yang Wang

  2. Effective Health Care Research Programme, RPC Programme, Consortium China, Chongqing, China

    Hui Li, Xiaojun Tang, Qin Liu & Yang Wang

Authors
  1. Hui Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xiaojun Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Qin Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yang Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Xiaojun Tang.

Additional information

Communicated by Guido Pozza.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Li, H., Tang, X., Liu, Q. et al. Association between type 2 diabetes and rs10811661 polymorphism upstream of CDKN2A/B: a meta-analysis. Acta Diabetol 50, 657–662 (2013). https://doi.org/10.1007/s00592-012-0400-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00592-012-0400-7

Keywords

Search

Navigation