PMID- 12589429
OWN - NLM
STAT- MEDLINE
DCOM- 20030516
LR  - 20221207
IS  - 0340-6717 (Print)
IS  - 0340-6717 (Linking)
VI  - 112
IP  - 4
DP  - 2003 Apr
TI  - The interleukin-6 (-174) G/C promoter polymorphism is associated with type-2 
      diabetes mellitus in Native Americans and Caucasians.
PG  - 409-13
AB  - Chronic low-grade activation of the immune system may play a role in the 
      pathogenesis of type-2 diabetes mellitus (T2DM). Interleukin-6 (IL6), a powerful 
      inducer of hepatic acute phase response, has been implicated in the etiology of 
      insulin resistance and T2DM. Recently, an IL6 promoter polymorphism (G/C) at 
      position -174 was found to be associated with measures of insulin sensitivity. 
      Because we have previously found an association between high IL6 levels and 
      insulin resistance in both Pima Indians - a population with high rates of insulin 
      resistance and T2DM - and Caucasians, we aimed to assess whether the IL6 promoter 
      polymorphism is associated with T2DM in these populations. We genotyped the IL6 
      (-174) G/C polymorphism using pyrosequencing in 463 Native Americans and by 
      PCR-RFLP in 329 Spanish Caucasians. Among the Spanish Caucasian subjects, there 
      was a significant difference in genotypic distribution between diabetic and 
      non-diabetic subjects (P=0.028); the GG genotype was more common in diabetic 
      (0.40) than in non-diabetic (0.29) subjects. The G allele was much more frequent 
      in the Native American sample, and among a sample of 143 cases and 145 controls, 
      the GG genotype was significantly more common in diabetic subjects (P=0.019). 
      When this sample population was stratified according to ethnic heritage, all 211 
      subjects who were of full Pima Indian heritage had the GG genotype, whereas in 
      the 77 American Indian subjects with non-Pima admixture, T2DM was associated with 
      IL6 genotype (P=0.001). These findings are consistent with a role for genetic 
      determinants of inflammation in the development of T2DM in both Native Americans 
      and Caucasians.
FAU - Vozarova, Barbora
AU  - Vozarova B
AD  - Clinical Diabetes and Nutrition Section, Phoenix Epidemiology and Clinical 
      Research Branch, National Institute of Diabetes and Digestive and Kidney 
      Diseases, National Institutes of Health, 4212 North 16th Street, Phoenix, AZ 
      85016, USA.
FAU - Fernandez-Real, Jose-Manuel
AU  - Fernandez-Real JM
FAU - Knowler, William C
AU  - Knowler WC
FAU - Gallart, Lluis
AU  - Gallart L
FAU - Hanson, Robert L
AU  - Hanson RL
FAU - Gruber, Jonathan D
AU  - Gruber JD
FAU - Ricart, Wilfredo
AU  - Ricart W
FAU - Vendrell, Joan
AU  - Vendrell J
FAU - Richart, Cristobal
AU  - Richart C
FAU - Tataranni, P Antonio
AU  - Tataranni PA
FAU - Wolford, Johanna K
AU  - Wolford JK
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20030214
PL  - Germany
TA  - Hum Genet
JT  - Human genetics
JID - 7613873
RN  - 0 (Interleukin-6)
RN  - 5Z93L87A1R (Guanine)
RN  - 8J337D1HZY (Cytosine)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Alleles
MH  - Asian People/genetics
MH  - Case-Control Studies
MH  - Cytosine
MH  - Diabetes Mellitus, Type 2/ethnology/*genetics
MH  - Female
MH  - Genotype
MH  - Guanine
MH  - Hispanic or Latino/*genetics
MH  - Humans
MH  - Indians, North American/*genetics
MH  - Interleukin-6/*genetics
MH  - Male
MH  - Middle Aged
MH  - Polymerase Chain Reaction
MH  - *Polymorphism, Genetic
MH  - Polymorphism, Restriction Fragment Length
MH  - Promoter Regions, Genetic/*genetics
MH  - White People/genetics
EDAT- 2003/02/18 04:00
MHDA- 2003/05/17 05:00
CRDT- 2003/02/18 04:00
PHST- 2002/11/18 00:00 [received]
PHST- 2002/12/30 00:00 [accepted]
PHST- 2003/02/18 04:00 [pubmed]
PHST- 2003/05/17 05:00 [medline]
PHST- 2003/02/18 04:00 [entrez]
AID - 10.1007/s00439-003-0912-x [doi]
PST - ppublish
SO  - Hum Genet. 2003 Apr;112(4):409-13. doi: 10.1007/s00439-003-0912-x. Epub 2003 Feb 
      14.