TY - JOUR
T1 - A C-reactive protein promoter polymorphism is associated with type 2 diabetes mellitus in Pima Indians
AU - Wolford, Johanna K
AU - Gruber, Jonathan D
AU - Ossowski, V
AU - Vozarova, Barbora
AU - Tataranni, P Antonio
AU - Bogardus, Clifton
AU - Hanson, Robert
PY - 2003
Y1 - 2003
N2 - Linkage analysis has identified a susceptibility locus for type 2 diabetes mellitus (T2DM) on chromosome 1q21?q23 in several
populations. Results from recent prospective studies indicate that increased levels of C-reactive protein (CRP), a marker of immune
system activation, are predictive of diabetes, independent of adiposity. Because CRP is located on 1q21, we considered it a potential
positional candidate gene for T2DM. We therefore evaluated CRP and the nearby serum amyloid P-component, APCS, which is
structurally similar to CRP, as candidate diabetes susceptibility genes. Approximately 10.9 kb of the CRP-APCS locus was screened
for polymorphisms using denaturing high performance liquid chromatography and direct sequencing. We identified 27 informative
polymorphisms, including 26 single nucleotide polymorphisms (SNPs) and 1 insertion/deletion, which were divided into 7 linkage
disequilibrium clusters. We genotyped representative SNPs in 1300 Pima samples and found a single variant in the CRP promoter
(SNP 133552) that was associated with T2DM (P ? 0:014), as well as a common haplotype (CGCG) that was associated with both
T2DM (P ? 0:029) and corrected insulin response, a surrogate measure of insulin secretion in non-diabetic subjects (P ? 0:050).
Linkage analyses that adjusted for the effect of these polymorphisms indicated that they do not in themselves account for the
observed linkage with T2DM on chromosome 1q. However, these findings suggest that variation within the CRP locus may play a
role in diabetes susceptibility in Pima Indians.
AB - Linkage analysis has identified a susceptibility locus for type 2 diabetes mellitus (T2DM) on chromosome 1q21?q23 in several
populations. Results from recent prospective studies indicate that increased levels of C-reactive protein (CRP), a marker of immune
system activation, are predictive of diabetes, independent of adiposity. Because CRP is located on 1q21, we considered it a potential
positional candidate gene for T2DM. We therefore evaluated CRP and the nearby serum amyloid P-component, APCS, which is
structurally similar to CRP, as candidate diabetes susceptibility genes. Approximately 10.9 kb of the CRP-APCS locus was screened
for polymorphisms using denaturing high performance liquid chromatography and direct sequencing. We identified 27 informative
polymorphisms, including 26 single nucleotide polymorphisms (SNPs) and 1 insertion/deletion, which were divided into 7 linkage
disequilibrium clusters. We genotyped representative SNPs in 1300 Pima samples and found a single variant in the CRP promoter
(SNP 133552) that was associated with T2DM (P ? 0:014), as well as a common haplotype (CGCG) that was associated with both
T2DM (P ? 0:029) and corrected insulin response, a surrogate measure of insulin secretion in non-diabetic subjects (P ? 0:050).
Linkage analyses that adjusted for the effect of these polymorphisms indicated that they do not in themselves account for the
observed linkage with T2DM on chromosome 1q. However, these findings suggest that variation within the CRP locus may play a
role in diabetes susceptibility in Pima Indians.
UR - http://ac.els-cdn.com.ezproxy.lib.monash.edu.au/S1096719202002305/1-s2.0-S1096719202002305-main.pdf?_tid=5877cde8-8870-11e3-b1d3-00000aab0f6c&acdnat=1
U2 - 10.1016/S1096-7192(02)00230-5
DO - 10.1016/S1096-7192(02)00230-5
M3 - Article
VL - 78
SP - 136
EP - 144
JO - Molecular Genetics and Metabolism
JF - Molecular Genetics and Metabolism
SN - 1096-7192
IS - 2
ER -