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01.07.2006 | Article

Common polymorphisms of calpain-10 are associated with abdominal obesity in subjects at high risk of type 2 diabetes

verfasst von: J. Pihlajamäki, U. Salmenniemi, M. Vänttinen, E. Ruotsalainen, J. Kuusisto, I. Vauhkonen, S. Kainulainen, M. C. Y. Ng, N. J. Cox, G. I. Bell, M. Laakso

Erschienen in: Diabetologia | Ausgabe 7/2006

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Abstract

Aims/hypothesis

The mechanisms by which the calpain-10 gene (CAPN10) affects the risk of type 2 diabetes are unclear. Therefore, we investigated the effects of four polymorphisms in CAPN10 (single nucleotide polymorphism [SNP]-43, SNP-44, Insertion/Deletion [Indel]-19 and SNP-63) on insulin secretion, insulin action and abdominal fat distribution in offspring of patients with type 2 diabetes.

Subjects and methods

Insulin secretion was determined by an IVGTT, insulin action by the hyperinsulinaemic–euglycaemic clamp and abdominal fat distribution by computed tomography in 158 non-diabetic offspring (age 34.9±6.3 years [mean±SD], BMI 26.2±4.9 kg/m²) of type 2 diabetic patients.

Results

SNP-43 (p=0.009 over the three genotypes, adjusted for age, sex, BMI and family relationship) and haplotypes carrying the A allele of SNP-43 were associated with intra-abdominal fat area. The A allele of SNP-43 was associated with intra-abdominal fat area in men (p=0.014) but not in women. SNP-44, InDel-19 and SNP-63 were not associated with intra-abdominal fat area or insulin action. Furthermore, we demonstrated in a separate sample of middle-aged men (n=234) who had a history of type 2 diabetes in first-degree relatives that the A allele of SNP-43 was associated with a large waist circumference, and high insulin levels in an OGTT.

Conclusions/interpretation

SNP-43 of CAPN10 may contribute to the risk of diabetes by regulating abdominal obesity in subjects with high risk of type 2 diabetes.

Despres JP (2001) Health consequences of visceral obesity. Ann Med 33:534–541PubMedCrossRef

Horikawa Y, Oda N, Cox NJ et al (2000) Genetic variation in the gene encoding calpain-10 is associated with type 2 diabetes mellitus. Nat Genet 26:163–175PubMedCrossRef

Ma H, Fukiage C, Kim YH et al (2001) Characterization and expression of calpain 10. A novel ubiquitous calpain with nuclear localization. J Biol Chem 276:28525–28531PubMedCrossRef

Baier LJ, Permana PA, Yang X et al (2000) A calpain-10 gene polymorphism is associated with reduced muscle mRNA levels and insulin resistance. J Clin Invest 106:R69–R73PubMedCrossRef

Garant MJ, Kao WH, Brancati F et al (2002) SNP43 of CAPN10 and the risk of type 2 Diabetes in African–Americans: the Atherosclerosis Risk in Communities Study. Diabetes 51:231–237PubMedCrossRef

Evans JC, Frayling TM, Cassell PG et al (2001) Studies of association between the gene for calpain-10 and type 2 diabetes mellitus in the United Kingdom. Am J Hum Genet 69:544–552PubMedCrossRef

Stumvoll M, Fritsche A, Madaus A et al (2001) Functional significance of the UCSNP-43 polymorphism in the CAPN10 gene for proinsulin processing and insulin secretion in nondiabetic Germans. Diabetes 50:2161–2163PubMedCrossRef

Hegele RA, Harris SB, Zinman B, Hanley AJ, Cao H (2001) Absence of association of type 2 diabetes with CAPN10 and PC-1 polymorphisms in Oji-Cree. Diabetes Care 24:1498–1499PubMedCrossRef

Elbein SC, Chu W, Ren Q et al (2002) Role of calpain-10 gene variants in familial type 2 diabetes in Caucasians. J Clin Endocrinol Metab 87:650–654PubMedCrossRef

10.

Fullerton SM, Bartoszewicz A, Ybazeta G et al (2002) Geographic and haplotype structure of candidate type 2 diabetes susceptibility variants at the calpain-10 locus. Am J Hum Genet 70:1096–1106PubMedCrossRef

11.

Cassell PG, Jackson AE, North BV et al (2002) Haplotype combinations of calpain 10 gene polymorphisms associate with increased risk of impaired glucose tolerance and type 2 diabetes in South Indians. Diabetes 51:1622–1628PubMedCrossRef

12.

Orho-Melander M, Klannemark M, Svensson MK, Ridderstrale M, Lindgren CM, Groop L (2002) Variants in the calpain-10 gene predispose to insulin resistance and elevated free fatty acid levels. Diabetes 51:2658–2664PubMedCrossRef

13.

Hoffstedt J, Naslund E, Arner P (2002) Calpain-10 gene polymorphism is associated with reduced beta(3)-adrenoceptor function in human fat cells. J Clin Endocrinol Metab 87:3362–3367PubMedCrossRef

14.

Lynn S, Evans JC, White C et al (2002) Variation in the calpain-10 gene affects blood glucose levels in the British population. Diabetes 51:247–250PubMedCrossRef

15.

Kittles R, Perola M, Peltonen L et al (1998) Dual origins of Finns revealed by Y chromosome haplotype variation. Am J Hum Genet 62:1171–1179PubMedCrossRef

16.

Salmenniemi U, Ruotsalainen E, Pihlajamäki J et al (2004) Multiple abnormalities in glucose and energy metabolism and coordinated changes in levels of adiponectin, cytokines, and adhesion molecules in subjects with metabolic syndrome. Circulation 110:3842–3848PubMedCrossRef

17.

Alberti KG, Zimmet PZ (1998) Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med 15:539–553PubMedCrossRef

18.

Galvin P, Ward G, Walters J et al (1992) A simple method for quantitation of insulin sensitivity and insulin release from an intravenous glucose tolerance test. Diabet Med 9:921–928PubMedCrossRef

19.

DeFronzo R, Tobin J, Andres R (1979) Glucose clamp technique: a method for quantifying insulin secretion and insulin resistance. Am J Physiol 237:E214–E223PubMed

20.

Laakso M, Uusitupa M, Takala J, Majander H, Reijonen T, Penttilä I (1988) Effects of hypocaloric diet and insulin therapy on metabolic control and mechanisms of hyperglycemia in obese non-insulin-dependent diabetic subjects. Metabolism 37:1092–1100PubMedCrossRef

21.

Ferrannini E (1988) The theoretical bases of indirect calorimetry: a review. Metabolism 37:287–301PubMedCrossRef

22.

Sjöstrom L, Kvist H, Cederblad A, Tylen U (1986) Determination of total adipose tissue and body fat in women by computed tomography, 40K, and tritium. Am J Physiol 250:E736–E745PubMed

23.

Laakso M, Sarlund H, Mykkänen L (1990) Insulin resistance is associated with lipid and lipoprotein abnormalities in subjects with varying degrees of glucose tolerance. Arteriosclerosis 10:223–231PubMed

24.

Abecasis GR, Cherny SS, Cookson WO, Cardon LR (2002) MERLIN—rapid analysis of dense genetic maps using sparse gene flow trees. Nat Genet 30:97–101PubMedCrossRef

25.

Abecasis GR, Cardon LR, Cookson WO (2000) A general test of association for quantitative traits in nuclear families. Am J Hum Genet 66:279–292PubMedCrossRef

26.

Weedon MN, Schwarz PE, Horikawa Y et al (2003) Meta-analysis and a large association study confirm a role for calpain-10 variation in type 2 diabetes susceptibility. Am J Hum Genet 73:1208–1212PubMedCrossRef

27.

Song Y, Niu T, Manson JE, Kwiatkowski DJ, Liu S (2004) 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 74:208–222PubMedCrossRef

28.

Carlsson E, Fredriksson J, Groop L, Ridderstrale M (2004) 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 89:3601–3605PubMedCrossRef

29.

Carlsson E, Poulsen P, Storgaard H et al (2005) Genetic and nongenetic regulation of CAPN10 mRNA expression in skeletal muscle. Diabetes 54:3015–3020PubMedCrossRef

30.

Vauhkonen I, Niskanen L, Vanninen E, Kainulainen S, Uusitupa M, Laakso M (1998) Defects in insulin secretion and insulin action in non-insulin-dependent diabetes mellitus are inherited. Metabolic studies on offspring of diabetic probands. J Clin Invest 101:86–96PubMedCrossRef

31.

Hoffstedt J, Ryden M, Lofgren P, Orho-Melander M, Groop L, Arner P (2002) Polymorphism in the Calpain 10 gene influences glucose metabolism in human fat cells. Diabetologia 45:276–282PubMedCrossRef

32.

Zierath JR, Livingston JN, Thorne A et al (1998) Regional difference in insulin inhibition of non-esterified fatty acid release from human adipocytes: relation to insulin receptor phosphorylation and intracellular signalling through the insulin receptor substrate-1 pathway. Diabetologia 41:1343–1354PubMedCrossRef

33.

Deeb S, Fajas L, Nemoto M et al (1998) A Pro12Ala substitution in the human peroxisome proliferator activated receptor gamma 2 is associated with decreased receptor activity, lower body mass index and improved insulin sensitivity. Nature Genetics 20:284–287PubMedCrossRef

34.

Altshuler D, Hirschhorn JN, Klannemark M et al (2000) The common PPARgamma Pro12Ala polymorphism is associated with decreased risk of type 2 diabetes. Nat Genet 26:76–80PubMedCrossRef

35.

Lindi V, Sivenius K, Niskanen L, Laakso M, Uusitupa MI (2001) Effect of the Pro12Ala polymorphism of the PPAR-gamma2 gene on long-term weight change in Finnish non-diabetic subjects. Diabetologia 44:925–926PubMedCrossRef

36.

Lindi VI, Uusitupa MI, Lindstrom J et al (2002) Association of the Pro12Ala polymorphism in the PPAR-gamma2 gene with 3-year incidence of type 2 diabetes and body weight change in the Finnish Diabetes Prevention Study. Diabetes 51:2581–2586PubMedCrossRef

37.

Rasmussen SK, Urhammer SA, Berglund L et al (2002) 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 51:3561–3567PubMedCrossRef

Titel: Common polymorphisms of calpain-10 are associated with abdominal obesity in subjects at high risk of type 2 diabetes
verfasst von: J. Pihlajamäki
U. Salmenniemi
M. Vänttinen
E. Ruotsalainen
J. Kuusisto
I. Vauhkonen
S. Kainulainen
M. C. Y. Ng
N. J. Cox
G. I. Bell
M. Laakso
Publikationsdatum: 01.07.2006
Verlag: Springer-Verlag
Erschienen in: Diabetologia / Ausgabe 7/2006
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-006-0270-z

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