Association of the calpain-10 gene with type 2 diabetes in Europeans: results of pooled and meta-analyses.
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.
Tsuchiya
Takafumi
T
Departments of Medicine and Human Genetics, The University of Chicago, 5841 S. Maryland Ave., MC1027, Chicago, IL 60637, USA.
Schwarz
Peter E H
PE
Bosque-Plata
Laura Del
LD
Geoffrey Hayes
M
M
Dina
Christian
C
Froguel
Philippe
P
Wayne Towers
G
G
Fischer
Sabine
S
Temelkova-Kurktschiev
Theodora
T
Rietzsch
Hannes
H
Graessler
Juergen
J
Vcelák
Josef
J
Palyzová
Daniela
D
Selisko
Thomas
T
Bendlová
Bela
B
Schulze
Jan
J
Julius
Ulrich
U
Hanefeld
Markolf
M
Weedon
Michael N
MN
Evans
Julie C
JC
Frayling
Timothy M
TM
Hattersley
Andrew T
AT
Orho-Melander
Marju
M
Groop
Leif
L
Malecki
Maciej T
MT
Hansen
Torben
T
Pedersen
Oluf
O
Fingerlin
Tasha E
TE
Boehnke
Michael
M
Hanis
Craig L
CL
Cox
Nancy J
NJ
Bell
Graeme I
GI
D002154:Calpain / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics*
D002154:Calpain; C415197:calpain 10