Relationship of the CDKAL1 and KCNQ1 gene polymorphisms to the age at diagnosis of type 2 diabetes in the Slovakian population


Authors: M. Dobríková 1;  M. Javorský 1;  V. Habálová 2;  L. Klimčáková 2;  M. Kozárová 1;  J. Židzik 2;  J. Halušková 2;  J. Šalagovič 2;  I. Tkáč 1
Authors‘ workplace: IV. interná klinika Lekárskej fakulty UPJŠ a Centra excelentnosti pre výskum aterosklerózy a jej komplikácií – srdcového a mozgového infarktu (CEVA) Lekárskej fakulty UPJŠ Košice, Slovenská republika, prednosta prof. MUDr. Ivan Tkáč, PhD. 1;  Ústav lekárskej biológie Lekárskej fakulty UPJŠ a Centra excelentnosti pre výskum aterosklerózy a jej komplikácií – srdcového a mozgového infarktu (CEVA) Lekárskej fakulty UPJŠ v Košice, Slovenská republika, prednosta prof. RNDr. Ján Šalagovič, PhD. 2
Published in: Vnitř Lék 2011; 57(2): 155-158
Category: Original Contributions

Overview

Background/aims:

The association of CDKAL1 and KCNQ1 genes with type 2 diabetes mellitus (DM2T) was confirmed by several genome-wide association studies in both Caucasian and Asian populations. For both genes, it is supposed that the risk of DM2T development is related to impaired insulin secretion. Based on assumption that the presence of risk allele might predispose to an earlier onset of DM2T, the aim of the present study was to assess the frequency of risk alleles of CDKAL1 rs7756992 and KCNQ1 rs163184 poly­morphisms and to analyze their association with the age at DM2T diagnosis in the Slovakian population.

Methods:
CDKAL1 rs7756992 A/G and KCNQ1 rs163184 G/T polymorphisms were genotyped using asymmetric PCR with subsequent melting curve analysis in a group of 538 patients with DM2T. Anthropometric and laboratory parameters were determined by using standard methods. Since two genes were analysed, the required level for statistical significance was defined as p < 0.025.

Results:
Risk homozygotes (GG) for KCNQ1 polymorphism had higher mean age of DM2T diagnosis by 2 years when compared to T-allele carriers (GT + TT) in a recessive model, but the difference did not reach the predefined level of statistical significance. No relationship of CDKAL1 polymorphism to the age at onset of DM2T diagnosis was observed.

Conclusions:
In the present study, no relationship of CDKAL1 and KCNQ1 polymorphisms to the earlier onset of type 2 diabetes was observed.

Key words:
type 2 diabetes mellitus – gene polymorphisms – CDKAL1KCNQ1 – age at diagnosis of diabetes


Sources

1. Ubeda M, Rukstalis JM, Habener JF. Inhibition of cyclin-dependent kinase 5 activity protects pancreatic beta cells from glucotoxicity. J Biol Chem 2006; 281: 28858–28864.

2. Ridderstråle M, Groop L. Genetic dissection of type 2 diabetes. Mol Cell Endocrinol 2009; 297: 10–17.

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

4. Wu Y, Li H, Loos RJ et al. Common variants in CDKAL1, CDKN2A/B, IGF2BP2, SLC30A8, and HHEX/IDE genes are associated with type 2 diabetes and impaired fasting glucose in a Chinese Han population. Diabetes 2008; 57: 2834–2842.

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

6. Steinthorsdottir V, Thorleifsson G, Reynisdottir I et al. A variant in CDKAL1 influences insulin response and risk of type 2 dia­betes. Nat Genet 2007; 39: 770–775.

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

8. Stančáková A, Kuulasmaa T, Paananen J et al. Association of 18 confirmed susceptibility loci for type 2 diabetes with indices of insulin release, proinsulin conversion, and insulin sensitivity in 5327 non-diabetic Finnish men. Diabetes 2009; 58: 2129–2136.

9. Unoki H, Takahashi A, Kawaguchi T et al. SNPs in KCNQ1 are associated with susceptibility to type 2 diabetes in East Asian and European populations. Nat Genet 2008; 40: 1098–1102.

10. Ullrich S, Su J, Ranta F et al. Effects of I( Ks) channels inhibitors in insulin-secreting INS-1 cells. Pflugers Arch 2005; 451: 428–436.

11. Yasuda K, Miyake K, Horikawa Y et al. Variants in KCNQ1 are associated with susceptibility to type 2 diabetes mellitus. Nat Genet 2008; 40: 1092–1097.

12. Lee Y, Kang ES, Kim SH et al. Association between polymorphisms in SLC30A8, HHEX, CDKN2A/B, IGF2BP2, FTO, WFS1, CDKAL1, KCNQ1 and type 2 diabetes in the Korean population. J Hum Genet 2008; 53: 991–998.

13. Müssig K, Staiger H, Machicao F et al. Association of type 2 diabetes candidate polymorphisms in KCNQ1 with incretin and insulin secretion. Diabetes 2009; 58: 1715–1720.

14. Cauchi S, Meyre D, Dina C et al. Transcription factor TCF7L2 genetics study in the French population: expression in human beta-cells and adipose tissue and strong association with type 2 diabetes. Dia­betes 2006; 55: 2903–2908.

15. Lehman DM, Hunt KJ, Leach RJ et al. Haplotypes of transcription factor 7-like 2 (TCF7L2) gene and its upstream region are associated with type 2 diabetes and age of onset in Mexican Americans. Diabetes 2007; 56: 389–393.

16. Kimber CH, Doney AS, Pearson ER et al. TCF7L2 in the Go-DARTS study: evidence for a gene dose effect on both diabetes susceptibility and control of glucose levels. Diabetologia 2007; 50: 1186–1191.

17. Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 1997; 20: 1183–1197.

18. Solé X, Guinó E, Valls J et al. SNPStats: a web tool for the analysis of association studies. Bioinformatics 2006; 22: 1928–1929.

19. Tong Y, Lin Y, Zhang Y et al. Association between TCF7L2 gene polymorphisms and susceptibility to type 2 diabetes mellitus: a large Human Genome Epidemiology (HuGE) review and meta-analysis. BMC Med Genet 2009; 10: 15.

Labels
Diabetology Endocrinology Internal medicine

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