Journal Mobile Options
Table of Contents
Vol. 19, No. 6, 2010
Issue release date: September 2010
Section title: Original Paper
Open Access Gateway
Med Princ Pract 2010;19:457–462
(DOI:10.1159/000320304)

Calpain-10 Gene Polymorphism in Type 2 Diabetes Mellitus Patients in the Gaza Strip

Zaharna M.M.a · Abed A.A.b · Sharif F.A.a
Departments of aMedical Technology and bBiology, Islamic University of Gaza, Gaza City, Palestine
email Corresponding Author

Abstract

Objective: To examine the role of calpain-10 SNP-44, -43, -63 and del/ins-19 in genetic susceptibility to type 2 diabetes mellitus (T2DM) and associations with triglycerides and total cholesterol in a group of subjects residing in the Gaza Strip. Subjects and Methods: Ninety-six individuals were examined: 48 T2DM patients and 48 controls. The groups were genotyped for calpain-10 SNP-44, -43, -63, and del/ins-19. Mutagenically separated polymerase chain reaction was used to examine SNP-44; del/ins-19 was examined by electrophoresis of the PCR product on agarose gel, while the restriction fragment length polymorphism method was used for SNP-43 and -63. Results: There was evidence that the C allele at SNP-44 played a possible role in susceptibility to T2DM (p = 0.01). T2DM patients with G/A genotype were found to have higher levels of total cholesterol in comparison to those homozygous for allele 1 (G/G) in SNP-43. Total cholesterol levels increased in T2DM patients who are homozygous for del/ins-19 allele 2, in T2DM patients with the 121/221 haplotype combination, and in control subjects with the haplotype combination 111/121. Conclusion: SNP-44 polymorphism of the calpain-10 gene has a significant association with T2DM patients in the Gaza strip. Certain polymorphisms of calpain-10 also have associations with the levels of total cholesterol in both T2DM patients and controls.

© 2010 S. Karger AG, Basel


  

Key Words

  • Calpain-10
  • Cholesterol
  • Gaza Strip
  • Triglycerides
  • Type 2 diabetes mellitus

References

  1. Hansen T: Genetics of type 2 diabetes. Curr Sci 2002;83:1477–1482.
  2. Gavin JR, Alberti KG, Davidson MB, DeFronzo RA, Drash A, Gabbe SG, Genuth S, Harris MI, Kahn R, Keen H, Knowler WC, Lebovitz H, Maclaren NK, Palmer JP, Raskin P, Rizza RA, Stern MP: Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care 2002;25:S5–S20.

    External Resources

  3. Venkat Narayan KM, Zhang P, Kanaya AM, Williams DE, Engelgau MM, Imperatore G, Ramachandran A: Diabetes: the pandemic and potential solutions; in Jamison DT, World Bank, Disease Control Priorities Project (eds): Disease Control Priorities in Developing Countries, ed 2. New York, Oxford University Press, 2006, pp 591–593.
  4. Ministry of Health-Palestine Health Information Center (MOH-PHIC): Non-communicable diseases: health status in Palestine 2005. 2006.
  5. Das SK: Genetic epidemiology of adult onset type 2 diabetes in Asian Indian population: past, present and future. Int J Hum Genet 2006;6:1–13.
  6. Toye A, Gauguier D: Genetics and functional genomics of type 2 diabetes mellitus. Genome Biol 2003;4:241.1–241.4.
  7. Horikawa Y, Oda N, Cox NJ, Li X, Orho-Melander M, Hara M, Hinokio Y, Lindner TH, Mashima H, Schwarz PE, Bosque-Plata LB, Horikawa Y, Oda Y, Yoshiuchi I, Colilla S, Polonsky KS, Wei S, Concannon P, Iwasaki N, Schulze J, Baier LJ, Bogardus C, Groop L, Boerwinkle E, Hanis CL, Bell GI: Genetic variation in the gene encoding calpain-10 is associated with type 2 diabetes mellitus. Nat Genet2000;26:163–175.
  8. Carlsson E, Fredriksson J, Groop L, Ridderstrale M: Variation in the calpain-10 gene is associated with elevated triglyceride levels and reduced adipose tissue messenger ribonucleic acid expression in obese Swedish subjects. J Clin Endocrinol Metab 2004;89:3601–3605.
  9. Daimon M, Oizumi T, Saitoh T, Kameda W, Yamaguchi H, Ohnuma H, Yamaguchi H, Ohnuma H, Igarashi M, Manaka H, Kato T: Calpain 10 gene polymorphisms are related, not to type 2 diabetes, but to increased serum cholesterol in Japanese. Diabetes Res Clin Pract 2002;56:147–152.
  10. Marshall C, Hitman GA, Partridge CJ, Clark A, Ma H, Shearer TR, Turner MD: Evidence that an isoform of calpain-10 Is a regulator of exocytosis in pancreatic β-cells. Mol Endocrinol 2005;19:213–224.
  11. Suzuki K, Hata S, Kawabata Y, Sorimachi H: Structure, activation, and biology of calpain. Diabetes2004;53:S12–S18.
  12. Rasmussen SK, Urhammer SA, Berglund L, Jensen JN, Hansen L, Echwald SM, Borch-Johnsen K, Horikawa Y, Mashima H, Lithell H, Cox NJ, Hansen T, Bell GI, Pedersen O: Variants within the calpain-10 gene on chromosome 2q37 (NIDDM1) and relationships to type 2 diabetes, insulin resistance, and impaired acute insulin secretion among Scandinavian Caucasians. Diabetes 2002;51:3561–3567.
  13. Evans JC, Frayling TM, Cassell PG, Saker PJ, Hitman GA, Walker M, Levy JC, O’Rahilly S, Subba Rao PV, Bennett AJ, Jones EC, Menzel S, Prestwich P, Simecek N, Wishart M, Dhillon R, Fletcher C, Millward A, Demaine A, Wilkin T, Horikawa Y, Cox NJ, Bell GI, Ellard S, McCarthy MI, Hattersley AT: Studies of association between the gene for calpain-10 and type 2 diabetes mellitus in the United Kingdom. Am J Hum Genet 2001;69:544–552.
  14. Malecki MT, Moczulski DK, Klupa T, Wanic K, Cyganek K, Frey J, Sieradzki J: Homozygous combination of calpain 10 gene haplotypes is associated with type 2 diabetes mellitus in a Polish population. Eur J Endocrinol 2002;146:695–699.
  15. Weedon MN, Schwarz PE, Horikawa Y, Iwasaki N, Illig T, Holle R, Rathmann W, Selisko T, Schulze J, Owen KR, Evans J, Bosque-Plata LD, Hitman G, Walker M, Levy JC, Sampson M, Bell GI, McCarthy MI, Hattersley AT, Frayling TM: Meta-analysis and a large association study confirm a role for calpain-10 variation in type 2 diabetes susceptibility. Am J Hum Genet 2003;73:1208–1212.
  16. Tsuchiya T, Schwarz P, Bosque-Plata L, Geoffrey Hayes M, Dina C, Froguel P, Wayne Towers G, Fischer S, Temelkova-Kurktschiev T, Rietzsch H, Graessler J, Vcelák J, Palyzová D, Selisko T, Bendlová B, Schulze J, Julius U, Hanefeld M, Weedon MN, Evans JC, Frayling TM, Hattersley AT, Orho-Melander M, Groop L, Malecki MT, Hansen T, Pedersen O, Fingerlin TE, Boehnke M, Hanis CL, Cox NJ, Bell GI: Association of the calpain-10 gene with type 2 diabetes in Europeans: results of pooled and meta-analysis. Mol Genet Metab2006;89:174–184.
  17. Cassell PG, Jackson AE, North BV, Evans JC, Syndercombe-Court D, Phillips C, Ramachandran A, Snehalatha C, Gelding SV, Vijayaravaghan S, Curtis D, Hitman GA: Haplotype combinations of calpain 10 gene polymorphisms associate with increased risk of impaired glucose tolerance and type 2 diabetes in South Indians. Diabetes 2002;51:1622–1628.
  18. Wu B, Takahashi J, Fu M, Cheng H, Matsumura S, Taniguchi H: Variants of calpain-10 gene and its association with type 2 diabetes mellitus in a Chinese population. Diabetes Res Clin Pract 2005;68:155–161.
  19. Fingerlin TE, Erdos MR, Watanabe RM, Wiles KR, Stringham HM, Mohlke KL, Silander K, Valle TT, Buchanan TA, Tuomilehto J, Bergman RN, Boehnke M, Collins FS: Variation in three single nucleotide polymorphisms in the calpain-10 gene not associated with type 2 diabetes in a large Finnish cohort. Diabetes 2002;51:1644–1648.
  20. Tsai HJ, Sun G, Weeks DE, Kaushal R, Wolujewicz M, McGarvey ST, Tufa J, Viali S, Deka R: Type 2 diabetes and three calpain-10 gene polymorphisms in Samoans: no evidence of association. Am J Hum Genet2001;69:1236–1244.
  21. Horikawa Y, Oda N, Yu LI, Imamura S, Fujiwara K, Makino M, Seino Y, Itoh M, Takeda J: Genetic variations in calpain-10 gene are not a major factor in the occurrence of type 2 diabetes in Japanese. J Clin Endocrinol Metab 2003;88:244–247.
  22. Song Y, Niu T, Manson JE, Kwiatkowski DJ, Liu S: Are variants in the CAPN10 gene related to risk of type 2 diabetes? A quantitative assessment of population and family-based association studies. Am J Hum Genet 2004;74:208–222.
  23. Thompson MW, Nussbaum RL, McInnes RR, Willard HF, Thompson JS, Boerkoel CF III: Thompson and Thompson Genetics in Medicine, ed 7. New York, Saunders, 2007, pp 199–200.

  

Author Contacts

Mr. Mazen M. Zaharna
Department of Medical Technology
Islamic University of Gaza
PO Box 108, Gaza City (Palestine)
Tel. +970 59 960 4870, Fax +970 8 286 0800, E-Mail mzaharna@iugaza.edu.ps

  

Article Information

Received: February 15, 2009
Revised: August 13, 2009
Published online: September 28, 2010
Number of Print Pages : 6
Number of Figures : 0, Number of Tables : 5, Number of References : 23

  

Publication Details

Medical Principles and Practice (International Journal of the Kuwait University Health Sciences Centre)

Vol. 19, No. 6, Year 2010 (Cover Date: September 2010)

Journal Editor: Owunwanne A. (Kuwait)
ISSN: 1011-7571 (Print), eISSN: 1423-0151 (Online)

For additional information: http://www.karger.com/MPP


Open Access License / Drug Dosage / Disclaimer

Open Access License: This is an Open Access article licensed under the terms of the Creative Commons Attribution-NonCommercial 3.0 Unported license (CC BY-NC) (www.karger.com/OA-license), applicable to the online version of the article only. Distribution permitted for non-commercial purposes only.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Hansen T: Genetics of type 2 diabetes. Curr Sci 2002;83:1477–1482.
  2. Gavin JR, Alberti KG, Davidson MB, DeFronzo RA, Drash A, Gabbe SG, Genuth S, Harris MI, Kahn R, Keen H, Knowler WC, Lebovitz H, Maclaren NK, Palmer JP, Raskin P, Rizza RA, Stern MP: Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care 2002;25:S5–S20.

    External Resources

  3. Venkat Narayan KM, Zhang P, Kanaya AM, Williams DE, Engelgau MM, Imperatore G, Ramachandran A: Diabetes: the pandemic and potential solutions; in Jamison DT, World Bank, Disease Control Priorities Project (eds): Disease Control Priorities in Developing Countries, ed 2. New York, Oxford University Press, 2006, pp 591–593.
  4. Ministry of Health-Palestine Health Information Center (MOH-PHIC): Non-communicable diseases: health status in Palestine 2005. 2006.
  5. Das SK: Genetic epidemiology of adult onset type 2 diabetes in Asian Indian population: past, present and future. Int J Hum Genet 2006;6:1–13.
  6. Toye A, Gauguier D: Genetics and functional genomics of type 2 diabetes mellitus. Genome Biol 2003;4:241.1–241.4.
  7. Horikawa Y, Oda N, Cox NJ, Li X, Orho-Melander M, Hara M, Hinokio Y, Lindner TH, Mashima H, Schwarz PE, Bosque-Plata LB, Horikawa Y, Oda Y, Yoshiuchi I, Colilla S, Polonsky KS, Wei S, Concannon P, Iwasaki N, Schulze J, Baier LJ, Bogardus C, Groop L, Boerwinkle E, Hanis CL, Bell GI: Genetic variation in the gene encoding calpain-10 is associated with type 2 diabetes mellitus. Nat Genet2000;26:163–175.
  8. Carlsson E, Fredriksson J, Groop L, Ridderstrale M: Variation in the calpain-10 gene is associated with elevated triglyceride levels and reduced adipose tissue messenger ribonucleic acid expression in obese Swedish subjects. J Clin Endocrinol Metab 2004;89:3601–3605.
  9. Daimon M, Oizumi T, Saitoh T, Kameda W, Yamaguchi H, Ohnuma H, Yamaguchi H, Ohnuma H, Igarashi M, Manaka H, Kato T: Calpain 10 gene polymorphisms are related, not to type 2 diabetes, but to increased serum cholesterol in Japanese. Diabetes Res Clin Pract 2002;56:147–152.
  10. Marshall C, Hitman GA, Partridge CJ, Clark A, Ma H, Shearer TR, Turner MD: Evidence that an isoform of calpain-10 Is a regulator of exocytosis in pancreatic β-cells. Mol Endocrinol 2005;19:213–224.
  11. Suzuki K, Hata S, Kawabata Y, Sorimachi H: Structure, activation, and biology of calpain. Diabetes2004;53:S12–S18.
  12. Rasmussen SK, Urhammer SA, Berglund L, Jensen JN, Hansen L, Echwald SM, Borch-Johnsen K, Horikawa Y, Mashima H, Lithell H, Cox NJ, Hansen T, Bell GI, Pedersen O: Variants within the calpain-10 gene on chromosome 2q37 (NIDDM1) and relationships to type 2 diabetes, insulin resistance, and impaired acute insulin secretion among Scandinavian Caucasians. Diabetes 2002;51:3561–3567.
  13. Evans JC, Frayling TM, Cassell PG, Saker PJ, Hitman GA, Walker M, Levy JC, O’Rahilly S, Subba Rao PV, Bennett AJ, Jones EC, Menzel S, Prestwich P, Simecek N, Wishart M, Dhillon R, Fletcher C, Millward A, Demaine A, Wilkin T, Horikawa Y, Cox NJ, Bell GI, Ellard S, McCarthy MI, Hattersley AT: Studies of association between the gene for calpain-10 and type 2 diabetes mellitus in the United Kingdom. Am J Hum Genet 2001;69:544–552.
  14. Malecki MT, Moczulski DK, Klupa T, Wanic K, Cyganek K, Frey J, Sieradzki J: Homozygous combination of calpain 10 gene haplotypes is associated with type 2 diabetes mellitus in a Polish population. Eur J Endocrinol 2002;146:695–699.
  15. Weedon MN, Schwarz PE, Horikawa Y, Iwasaki N, Illig T, Holle R, Rathmann W, Selisko T, Schulze J, Owen KR, Evans J, Bosque-Plata LD, Hitman G, Walker M, Levy JC, Sampson M, Bell GI, McCarthy MI, Hattersley AT, Frayling TM: Meta-analysis and a large association study confirm a role for calpain-10 variation in type 2 diabetes susceptibility. Am J Hum Genet 2003;73:1208–1212.
  16. Tsuchiya T, Schwarz P, Bosque-Plata L, Geoffrey Hayes M, Dina C, Froguel P, Wayne Towers G, Fischer S, Temelkova-Kurktschiev T, Rietzsch H, Graessler J, Vcelák J, Palyzová D, Selisko T, Bendlová B, Schulze J, Julius U, Hanefeld M, Weedon MN, Evans JC, Frayling TM, Hattersley AT, Orho-Melander M, Groop L, Malecki MT, Hansen T, Pedersen O, Fingerlin TE, Boehnke M, Hanis CL, Cox NJ, Bell GI: Association of the calpain-10 gene with type 2 diabetes in Europeans: results of pooled and meta-analysis. Mol Genet Metab2006;89:174–184.
  17. Cassell PG, Jackson AE, North BV, Evans JC, Syndercombe-Court D, Phillips C, Ramachandran A, Snehalatha C, Gelding SV, Vijayaravaghan S, Curtis D, Hitman GA: Haplotype combinations of calpain 10 gene polymorphisms associate with increased risk of impaired glucose tolerance and type 2 diabetes in South Indians. Diabetes 2002;51:1622–1628.
  18. Wu B, Takahashi J, Fu M, Cheng H, Matsumura S, Taniguchi H: Variants of calpain-10 gene and its association with type 2 diabetes mellitus in a Chinese population. Diabetes Res Clin Pract 2005;68:155–161.
  19. Fingerlin TE, Erdos MR, Watanabe RM, Wiles KR, Stringham HM, Mohlke KL, Silander K, Valle TT, Buchanan TA, Tuomilehto J, Bergman RN, Boehnke M, Collins FS: Variation in three single nucleotide polymorphisms in the calpain-10 gene not associated with type 2 diabetes in a large Finnish cohort. Diabetes 2002;51:1644–1648.
  20. Tsai HJ, Sun G, Weeks DE, Kaushal R, Wolujewicz M, McGarvey ST, Tufa J, Viali S, Deka R: Type 2 diabetes and three calpain-10 gene polymorphisms in Samoans: no evidence of association. Am J Hum Genet2001;69:1236–1244.
  21. Horikawa Y, Oda N, Yu LI, Imamura S, Fujiwara K, Makino M, Seino Y, Itoh M, Takeda J: Genetic variations in calpain-10 gene are not a major factor in the occurrence of type 2 diabetes in Japanese. J Clin Endocrinol Metab 2003;88:244–247.
  22. Song Y, Niu T, Manson JE, Kwiatkowski DJ, Liu S: Are variants in the CAPN10 gene related to risk of type 2 diabetes? A quantitative assessment of population and family-based association studies. Am J Hum Genet 2004;74:208–222.
  23. Thompson MW, Nussbaum RL, McInnes RR, Willard HF, Thompson JS, Boerkoel CF III: Thompson and Thompson Genetics in Medicine, ed 7. New York, Saunders, 2007, pp 199–200.