PMID- 15562008
OWN - NLM
STAT- MEDLINE
DCOM- 20050324
LR  - 20221207
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 90
IP  - 2
DP  - 2005 Feb
TI  - Molecular screening and association analyses of the interleukin 6 receptor gene 
      variants with type 2 diabetes, diabetic nephropathy, and insulin sensitivity.
PG  - 1123-9
AB  - IL-6 levels and polymorphisms have been implicated in type 2 diabetes mellitus 
      (T2DM) and insulin resistance. The IL-6 receptor (IL-6R) comprises two subunits, 
      IL-6R and gp130, of which IL-6R confers specificity to IL-6 action and is located 
      in a region of replicated linkage to T2DM on chromosome 1q21. We screened this 
      gene for variation in Northern European Caucasian and African-American ethnic 
      groups. We identified 11 variants with a minor allele frequency over 5%, 
      including two amino acid changes (D358A and V385I) and four variants in the 3' 
      untranslated region. No variant was associated with obesity or measures of 
      insulin sensitivity, but two single nucleotide polymorphisms in the 3' 
      untranslated region showed a trend to an association with T2DM in all Caucasians, 
      and three single nucleotide polymorphisms, including D358A, showed a trend (P < 
      0.06) to an association with T2DM among the subset of Northern European 
      Caucasians. Variant V385I was unique to African-Americans and was significantly 
      associated with diabetes and diabetic nephropathy (P < 0.05). Among individuals 
      heterozygous for the four variants in the transcribed sequence, one allele was 
      significantly overrepresented, thus suggesting the existence of a regulatory 
      variant controlling mRNA stability or expression. IL-6R is not likely to explain 
      the linkage to diabetes in this region, but our work supports a minor role of 
      variants in T2DM risk and suggests that sequence variants may alter IL-6R mRNA 
      levels and possibly levels of soluble IL-6R.
FAU - Wang, Hua
AU  - Wang H
AD  - Division of Endocrinology and Metabolism, University of Arkansas for Medical 
      Sciences, Little Rock, Arkansas 72205, USA.
FAU - Zhang, Zhengxian
AU  - Zhang Z
FAU - Chu, Winston
AU  - Chu W
FAU - Hale, Terri
AU  - Hale T
FAU - Cooper, Judith J
AU  - Cooper JJ
FAU - Elbein, Steven C
AU  - Elbein SC
LA  - eng
GR  - R01 DK039311-24/DK/NIDDK NIH HHS/United States
GR  - DK054636/DK/NIDDK NIH HHS/United States
GR  - DK039311/DK/NIDDK NIH HHS/United States
GR  - R01 DK039311/DK/NIDDK NIH HHS/United States
GR  - M01RR14288/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20041123
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (3' Untranslated Regions)
RN  - 0 (Receptors, Interleukin-6)
SB  - IM
MH  - 3' Untranslated Regions/genetics
MH  - Amino Acid Substitution
MH  - Arkansas
MH  - Black People
MH  - Diabetes Mellitus, Type 2/diagnosis/*genetics
MH  - Diabetic Nephropathies/diagnosis/*genetics
MH  - Exons/genetics
MH  - Gene Frequency
MH  - Genetic Testing/methods
MH  - *Genetic Variation
MH  - Humans
MH  - Insulin Resistance/*genetics
MH  - Linkage Disequilibrium
MH  - Microsatellite Repeats
MH  - Polymorphism, Genetic
MH  - Polymorphism, Single Nucleotide
MH  - Receptors, Interleukin-6/*genetics
MH  - Utah
MH  - White People
EDAT- 2004/11/25 09:00
MHDA- 2005/03/25 09:00
CRDT- 2004/11/25 09:00
PHST- 2004/11/25 09:00 [pubmed]
PHST- 2005/03/25 09:00 [medline]
PHST- 2004/11/25 09:00 [entrez]
AID - jc.2004-1606 [pii]
AID - 10.1210/jc.2004-1606 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2005 Feb;90(2):1123-9. doi: 10.1210/jc.2004-1606. Epub 
      2004 Nov 23.