Association of the calpain-10 gene with type 2 diabetes in Europeans: results of pooled and meta-analyses

Takafumi Tsuchiya; Peter E H Schwarz; Laura Del Bosque-Plata; M Geoffrey Hayes; Christian Dina; Philippe Froguel; G Wayne Towers; Sabine Fischer; Theodora Temelkova-Kurktschiev; Hannes Rietzsch; Juergen Graessler; Josef Vcelák; Daniela Palyzová; Thomas Selisko; Bela Bendlová; Jan Schulze; Ulrich Julius; Markolf Hanefeld; Michael N Weedon; Julie C Evans; Timothy M Frayling; Andrew T Hattersley; Marju Orho-Melander; Leif Groop; Maciej T Malecki; Torben Hansen; Oluf Pedersen; Tasha E Fingerlin; Michael Boehnke; Craig L Hanis; Nancy J Cox; Graeme I Bell

doi:10.1016/j.ymgme.2006.05.013

Association of the calpain-10 gene with type 2 diabetes in Europeans: results of pooled and meta-analyses

Takafumi Tsuchiya, Peter E H Schwarz, Laura Del Bosque-Plata, M Geoffrey Hayes, Christian Dina, Philippe Froguel, G Wayne Towers, Sabine Fischer, Theodora Temelkova-Kurktschiev, Hannes Rietzsch, Juergen Graessler, Josef Vcelák, Daniela Palyzová, Thomas Selisko, Bela Bendlová, Jan Schulze, Ulrich Julius, Markolf Hanefeld, Michael N Weedon, Julie C EvansTimothy M Frayling, Andrew T Hattersley, Marju Orho-Melander, Leif Groop, Maciej T Malecki, Torben Hansen, Oluf Pedersen, Tasha E Fingerlin, Michael Boehnke, Craig L Hanis, Nancy J Cox, Graeme I Bell

73 Citations (Scopus)

Abstract

We conducted pooled and meta-analyses of the association of the calpain-10 gene (CAPN10) polymorphisms SNP-43, Indel-19 and SNP-63 individually and as haplotypes with type 2 diabetes (T2D) in 3237 patients and 2935 controls of European ancestry. In the pooled analyses, the common SNP-43*G allele was associated with modest but statistically significant increased risk of T2D (odds ratio (OR)=1.11 (95% confidence interval (CI), 1.02-1.20), P=0.01). Two haplotype combinations were associated with increased risk of T2D (1-2-1/1-2-1, OR=1.20 (1.03-1.41), P=0.02; and 1-1-2/1-2-1, OR=1.26 (1.01-1.59), P=0.04) and one with decreased risk (1-1-1/2-2-1, OR=0.86 (0.75-0.99), P=0.03). The meta-analysis also showed a significant effect of the 1-2-1/1-2-1 haplogenotype on risk (OR=1.25 (1.05-1.50), P=0.01). However, there was evidence for heterogeneity with respect to this effect (P=0.06). The heterogeneity appeared to be due to data sets in which the cases were selected from samples used in linkage studies of T2D. Using only the population-based case-control samples removed the heterogeneity (P=0.89) and strengthened the evidence for association with T2D in both the pooled (SNP-43*G, OR=1.19 (1.07-1.32), P=0.001; 1-2-1/1-2-1 haplogenotype, OR=1.46 (1.19-1.78), P=0.0003; 1-1-2/1-2-1 haplogenotype, OR=1.52 (1.12-2.06), P=0.007; and 1-1-1/2-2-1 haplogenotype, OR=0.83 (0.70-0.99), P=0.03) and the meta-analysis (SNP-43*G, OR=1.18 (1.05-1.32), P=0.005; 1-2-1/1-2-1 haplogenotype, OR=1.68 (1.33-2.11), P=0.00001). The pooled and meta-analyses as well as the linkage disequilibrium and haplotype diversity studies suggest a role for genetic variation in CAPN10 affecting risk of T2D in Europeans.

Original language	English
Journal	Molecular Genetics and Metabolism
Volume	89
Issue number	1-2
Pages (from-to)	174-84
Number of pages	11
ISSN	1096-7192
DOIs	https://doi.org/10.1016/j.ymgme.2006.05.013
Publication status	Published - 2006

Keywords

Calpain
Diabetes Mellitus, Type 2
European Continental Ancestry Group
Haplotypes
Humans
Linkage Disequilibrium
Polymorphism, Single Nucleotide

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.ymgme.2006.05.013

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Tsuchiya, T., Schwarz, P. E. H., Bosque-Plata, L. D., 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, M. N., ... Bell, G. I. (2006). Association of the calpain-10 gene with type 2 diabetes in Europeans: results of pooled and meta-analyses. Molecular Genetics and Metabolism, 89(1-2), 174-84. https://doi.org/10.1016/j.ymgme.2006.05.013

Tsuchiya, T, Schwarz, PEH, Bosque-Plata, LD, 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 2006, 'Association of the calpain-10 gene with type 2 diabetes in Europeans: results of pooled and meta-analyses', Molecular Genetics and Metabolism, vol. 89, no. 1-2, pp. 174-84. https://doi.org/10.1016/j.ymgme.2006.05.013

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title = "Association of the calpain-10 gene with type 2 diabetes in Europeans: results of pooled and meta-analyses",

abstract = "We conducted pooled and meta-analyses of the association of the calpain-10 gene (CAPN10) polymorphisms SNP-43, Indel-19 and SNP-63 individually and as haplotypes with type 2 diabetes (T2D) in 3237 patients and 2935 controls of European ancestry. In the pooled analyses, the common SNP-43*G allele was associated with modest but statistically significant increased risk of T2D (odds ratio (OR)=1.11 (95% confidence interval (CI), 1.02-1.20), P=0.01). Two haplotype combinations were associated with increased risk of T2D (1-2-1/1-2-1, OR=1.20 (1.03-1.41), P=0.02; and 1-1-2/1-2-1, OR=1.26 (1.01-1.59), P=0.04) and one with decreased risk (1-1-1/2-2-1, OR=0.86 (0.75-0.99), P=0.03). The meta-analysis also showed a significant effect of the 1-2-1/1-2-1 haplogenotype on risk (OR=1.25 (1.05-1.50), P=0.01). However, there was evidence for heterogeneity with respect to this effect (P=0.06). The heterogeneity appeared to be due to data sets in which the cases were selected from samples used in linkage studies of T2D. Using only the population-based case-control samples removed the heterogeneity (P=0.89) and strengthened the evidence for association with T2D in both the pooled (SNP-43*G, OR=1.19 (1.07-1.32), P=0.001; 1-2-1/1-2-1 haplogenotype, OR=1.46 (1.19-1.78), P=0.0003; 1-1-2/1-2-1 haplogenotype, OR=1.52 (1.12-2.06), P=0.007; and 1-1-1/2-2-1 haplogenotype, OR=0.83 (0.70-0.99), P=0.03) and the meta-analysis (SNP-43*G, OR=1.18 (1.05-1.32), P=0.005; 1-2-1/1-2-1 haplogenotype, OR=1.68 (1.33-2.11), P=0.00001). The pooled and meta-analyses as well as the linkage disequilibrium and haplotype diversity studies suggest a role for genetic variation in CAPN10 affecting risk of T2D in Europeans.",

keywords = "Calpain, Diabetes Mellitus, Type 2, European Continental Ancestry Group, Haplotypes, Humans, Linkage Disequilibrium, Polymorphism, Single Nucleotide",

author = "Takafumi Tsuchiya and Schwarz, {Peter E H} and Bosque-Plata, {Laura Del} and {Geoffrey Hayes}, M and Christian Dina and Philippe Froguel and {Wayne Towers}, G and Sabine Fischer and Theodora Temelkova-Kurktschiev and Hannes Rietzsch and Juergen Graessler and Josef Vcel{\'a}k and Daniela Palyzov{\'a} and Thomas Selisko and Bela Bendlov{\'a} and Jan Schulze and Ulrich Julius and Markolf Hanefeld and Weedon, {Michael N} and Evans, {Julie C} and Frayling, {Timothy M} and Hattersley, {Andrew T} and Marju Orho-Melander and Leif Groop and Malecki, {Maciej T} and Torben Hansen and Oluf Pedersen and Fingerlin, {Tasha E} and Michael Boehnke and Hanis, {Craig L} and Cox, {Nancy J} and Bell, {Graeme I}",

year = "2006",

doi = "10.1016/j.ymgme.2006.05.013",

language = "English",

volume = "89",

pages = "174--84",

journal = "Molecular Genetics and Metabolism",

issn = "1096-7192",

publisher = "Academic Press",

number = "1-2",

}

TY - JOUR

T1 - Association of the calpain-10 gene with type 2 diabetes in Europeans

T2 - results of pooled and meta-analyses

AU - Tsuchiya, Takafumi

AU - Schwarz, Peter E H

AU - Bosque-Plata, Laura Del

AU - Geoffrey Hayes, M

AU - Dina, Christian

AU - Froguel, Philippe

AU - Wayne Towers, G

AU - Fischer, Sabine

AU - Temelkova-Kurktschiev, Theodora

AU - Rietzsch, Hannes

AU - Graessler, Juergen

AU - Vcelák, Josef

AU - Palyzová, Daniela

AU - Selisko, Thomas

AU - Bendlová, Bela

AU - Schulze, Jan

AU - Julius, Ulrich

AU - Hanefeld, Markolf

AU - Weedon, Michael N

AU - Evans, Julie C

AU - Frayling, Timothy M

AU - Hattersley, Andrew T

AU - Orho-Melander, Marju

AU - Groop, Leif

AU - Malecki, Maciej T

AU - Hansen, Torben

AU - Pedersen, Oluf

AU - Fingerlin, Tasha E

AU - Boehnke, Michael

AU - Hanis, Craig L

AU - Cox, Nancy J

AU - Bell, Graeme I

PY - 2006

Y1 - 2006

N2 - We conducted pooled and meta-analyses of the association of the calpain-10 gene (CAPN10) polymorphisms SNP-43, Indel-19 and SNP-63 individually and as haplotypes with type 2 diabetes (T2D) in 3237 patients and 2935 controls of European ancestry. In the pooled analyses, the common SNP-43*G allele was associated with modest but statistically significant increased risk of T2D (odds ratio (OR)=1.11 (95% confidence interval (CI), 1.02-1.20), P=0.01). Two haplotype combinations were associated with increased risk of T2D (1-2-1/1-2-1, OR=1.20 (1.03-1.41), P=0.02; and 1-1-2/1-2-1, OR=1.26 (1.01-1.59), P=0.04) and one with decreased risk (1-1-1/2-2-1, OR=0.86 (0.75-0.99), P=0.03). The meta-analysis also showed a significant effect of the 1-2-1/1-2-1 haplogenotype on risk (OR=1.25 (1.05-1.50), P=0.01). However, there was evidence for heterogeneity with respect to this effect (P=0.06). The heterogeneity appeared to be due to data sets in which the cases were selected from samples used in linkage studies of T2D. Using only the population-based case-control samples removed the heterogeneity (P=0.89) and strengthened the evidence for association with T2D in both the pooled (SNP-43*G, OR=1.19 (1.07-1.32), P=0.001; 1-2-1/1-2-1 haplogenotype, OR=1.46 (1.19-1.78), P=0.0003; 1-1-2/1-2-1 haplogenotype, OR=1.52 (1.12-2.06), P=0.007; and 1-1-1/2-2-1 haplogenotype, OR=0.83 (0.70-0.99), P=0.03) and the meta-analysis (SNP-43*G, OR=1.18 (1.05-1.32), P=0.005; 1-2-1/1-2-1 haplogenotype, OR=1.68 (1.33-2.11), P=0.00001). The pooled and meta-analyses as well as the linkage disequilibrium and haplotype diversity studies suggest a role for genetic variation in CAPN10 affecting risk of T2D in Europeans.

AB - We conducted pooled and meta-analyses of the association of the calpain-10 gene (CAPN10) polymorphisms SNP-43, Indel-19 and SNP-63 individually and as haplotypes with type 2 diabetes (T2D) in 3237 patients and 2935 controls of European ancestry. In the pooled analyses, the common SNP-43*G allele was associated with modest but statistically significant increased risk of T2D (odds ratio (OR)=1.11 (95% confidence interval (CI), 1.02-1.20), P=0.01). Two haplotype combinations were associated with increased risk of T2D (1-2-1/1-2-1, OR=1.20 (1.03-1.41), P=0.02; and 1-1-2/1-2-1, OR=1.26 (1.01-1.59), P=0.04) and one with decreased risk (1-1-1/2-2-1, OR=0.86 (0.75-0.99), P=0.03). The meta-analysis also showed a significant effect of the 1-2-1/1-2-1 haplogenotype on risk (OR=1.25 (1.05-1.50), P=0.01). However, there was evidence for heterogeneity with respect to this effect (P=0.06). The heterogeneity appeared to be due to data sets in which the cases were selected from samples used in linkage studies of T2D. Using only the population-based case-control samples removed the heterogeneity (P=0.89) and strengthened the evidence for association with T2D in both the pooled (SNP-43*G, OR=1.19 (1.07-1.32), P=0.001; 1-2-1/1-2-1 haplogenotype, OR=1.46 (1.19-1.78), P=0.0003; 1-1-2/1-2-1 haplogenotype, OR=1.52 (1.12-2.06), P=0.007; and 1-1-1/2-2-1 haplogenotype, OR=0.83 (0.70-0.99), P=0.03) and the meta-analysis (SNP-43*G, OR=1.18 (1.05-1.32), P=0.005; 1-2-1/1-2-1 haplogenotype, OR=1.68 (1.33-2.11), P=0.00001). The pooled and meta-analyses as well as the linkage disequilibrium and haplotype diversity studies suggest a role for genetic variation in CAPN10 affecting risk of T2D in Europeans.

KW - Calpain

KW - Diabetes Mellitus, Type 2

KW - European Continental Ancestry Group

KW - Haplotypes

KW - Humans

KW - Linkage Disequilibrium

KW - Polymorphism, Single Nucleotide

U2 - 10.1016/j.ymgme.2006.05.013

DO - 10.1016/j.ymgme.2006.05.013

M3 - Journal article

C2 - 16837224

SN - 1096-7192

VL - 89

SP - 174

EP - 184

JO - Molecular Genetics and Metabolism

JF - Molecular Genetics and Metabolism

IS - 1-2

ER -

Association of the calpain-10 gene with type 2 diabetes in Europeans: results of pooled and meta-analyses

Abstract

Keywords

UN SDGs

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