PMID- 12618085
OWN - NLM
STAT- MEDLINE
DCOM- 20030508
LR  - 20191106
IS  - 1096-7192 (Print)
IS  - 1096-7192 (Linking)
VI  - 78
IP  - 2
DP  - 2003 Feb
TI  - A C-reactive protein promoter polymorphism is associated with type 2 diabetes 
      mellitus in Pima Indians.
PG  - 136-44
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 10.9kb 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 approximately 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.
FAU - Wolford, Johanna K
AU  - Wolford JK
AD  - Clinical Diabetes and Nutrition Section, Phoenix Epidemiology and Research 
      Branch, National Institute of Diabetes and Digestive and Kidney Diseases, 
      National Institutes of Health, Phoenix, AZ 85016, USA. jwolford@exchange.nih.gov
FAU - Gruber, Jonathan D
AU  - Gruber JD
FAU - Ossowski, Victoria M
AU  - Ossowski VM
FAU - Vozarova, Barbora
AU  - Vozarova B
FAU - Antonio Tataranni, P
AU  - Antonio Tataranni P
FAU - Bogardus, Clifton
AU  - Bogardus C
FAU - Hanson, Robert L
AU  - Hanson RL
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Mol Genet Metab
JT  - Molecular genetics and metabolism
JID - 9805456
RN  - 0 (DNA Primers)
RN  - 9007-41-4 (C-Reactive Protein)
SB  - IM
EIN - Mol Genet Metab. 2003 Jul;79(3):231
MH  - Base Sequence
MH  - C-Reactive Protein/*genetics
MH  - DNA Primers
MH  - Diabetes Mellitus, Type 2/*genetics
MH  - Humans
MH  - Indians, North American/*genetics
MH  - *Polymorphism, Single Nucleotide
MH  - *Promoter Regions, Genetic
EDAT- 2003/03/06 04:00
MHDA- 2003/05/09 05:00
CRDT- 2003/03/06 04:00
PHST- 2003/03/06 04:00 [pubmed]
PHST- 2003/05/09 05:00 [medline]
PHST- 2003/03/06 04:00 [entrez]
AID - S1096719202002305 [pii]
AID - 10.1016/s1096-7192(02)00230-5 [doi]
PST - ppublish
SO  - Mol Genet Metab. 2003 Feb;78(2):136-44. doi: 10.1016/s1096-7192(02)00230-5.