PMID- 21756351
OWN - NLM
STAT- MEDLINE
DCOM- 20111104
LR  - 20211020
IS  - 1471-2350 (Electronic)
IS  - 1471-2350 (Linking)
VI  - 12
DP  - 2011 Jul 14
TI  - Genetic polymorphisms of innate immunity-related inflammatory pathways and their 
      association with factors related to type 2 diabetes.
PG  - 95
LID - 10.1186/1471-2350-12-95 [doi]
AB  - BACKGROUND: Type 2 diabetes mellitus (T2DM) has been linked to a state of 
      pre-clinical chronic inflammation resulting from abnormalities in the innate 
      immune pathway. Serum levels of pro-inflammatory cytokines and acute-phase 
      proteins, collectively known as 'inflammatory network', are elevated in the pre-, 
      or early, stages of T2DM and increase with disease progression. Genetic variation 
      can affect the innate immune response to certain environmental factors, and may, 
      therefore, determine an individual's lifetime risk of disease. METHODS: We 
      conducted a cross-sectional study in 6,720 subjects from the Twins UK Registry to 
      evaluate the association between 18 single nucleotide polymorphisms (SNPs) in 
      five genes (TLR4, IL1A, IL6, TNFA, and CRP) along the innate immunity-related 
      inflammatory pathway and biomarkers of predisposition to T2DM [fasting insulin 
      and glucose, HDL- and LDL- cholesterols, triglycerides (TGs), amyloid-A, 
      sensitive C-reactive protein (sCRP) and vitamin D binding protein (VDBP) and body 
      mass index (BMI)]. RESULTS: Of 18 the SNPs examined for their association with 
      nine metabolic phenotypes of interest, six were significantly associated with 
      five metabolic phenotypes (Bonferroni correction, P </= 0.0027). Fasting insulin 
      was associated with SNPs in IL6 and TNFA, serum HDL-C with variants of TNFA and 
      CRP and serum sCRP level with SNPs in CRP. Cross-correlation analysis among the 
      different metabolic factors related to risk of T2DM showed several significant 
      associations. For example, BMI was directly correlated with glucose (r = 0.11), 
      insulin (r = 0.15), sCRP (r = 0.23), LDL-C (r = 0.067) and TGs (r = 0.18) but 
      inversely with HDL-C (r = -0.14). sCRP was also positively correlated (P < 
      0.0001) with insulin (r = 0.17), amyloid-A (r = 0.39), TGs (r = 0.26), and VDBP 
      (r = 0.36) but inversely with HDL-C (r = -0.12). CONCLUSION: Genetic variants in 
      the innate immunity pathway and its related inflammatory cascade is associated 
      with some metabolic risk factors for T2DM; an observation that may provide a 
      rationale for further studying their role as biomarkers for disease early risk 
      prediction.
FAU - Arora, Paul
AU  - Arora P
AD  - Office for Biotechnology, Genomics and Population Health, Public Health Agency of 
      Canada, 180 Queen Street West, Toronto, M5V 3L7, Canada.
FAU - Garcia-Bailo, Bibiana
AU  - Garcia-Bailo B
FAU - Dastani, Zari
AU  - Dastani Z
FAU - Brenner, Darren
AU  - Brenner D
FAU - Villegas, Andre
AU  - Villegas A
FAU - Malik, Suneil
AU  - Malik S
FAU - Spector, Timothy D
AU  - Spector TD
FAU - Richards, Brent
AU  - Richards B
FAU - El-Sohemy, Ahmed
AU  - El-Sohemy A
FAU - Karmali, Mohamed
AU  - Karmali M
FAU - Badawi, Alaa
AU  - Badawi A
LA  - eng
GR  - G20234/Biotechnology and Biological Sciences Research Council/United Kingdom
GR  - Arthritis Research UK/United Kingdom
GR  - Canadian Institutes of Health Research/Canada
GR  - Wellcome Trust/United Kingdom
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Twin Study
DEP - 20110714
PL  - England
TA  - BMC Med Genet
JT  - BMC medical genetics
JID - 100968552
RN  - 0 (Acute-Phase Proteins)
RN  - 0 (Blood Glucose)
RN  - 0 (CRP protein, human)
RN  - 0 (Cytokines)
RN  - 0 (IL1A protein, human)
RN  - 0 (IL6 protein, human)
RN  - 0 (Insulin)
RN  - 0 (Interleukin-1alpha)
RN  - 0 (Interleukin-6)
RN  - 0 (Receptors, Immunologic)
RN  - 0 (Serum Amyloid A Protein)
RN  - 0 (TLR4 protein, human)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Triglycerides)
RN  - 0 (Vitamin D-Binding Protein)
RN  - 9007-41-4 (C-Reactive Protein)
RN  - 97C5T2UQ7J (Cholesterol)
SB  - IM
MH  - Acute-Phase Proteins/metabolism
MH  - Blood Glucose
MH  - Body Mass Index
MH  - C-Reactive Protein/metabolism
MH  - Cholesterol/blood
MH  - Cross-Sectional Studies
MH  - Cytokines/blood
MH  - Diabetes Mellitus, Type 2/*genetics/immunology
MH  - Female
MH  - Humans
MH  - Immunity, Innate/*genetics
MH  - Insulin/blood
MH  - Interleukin-1alpha/genetics
MH  - Interleukin-6/genetics
MH  - Linear Models
MH  - Polymorphism, Single Nucleotide/*genetics
MH  - Receptors, Immunologic/genetics
MH  - Serum Amyloid A Protein/metabolism
MH  - Toll-Like Receptor 4/genetics
MH  - Triglycerides/blood
MH  - United Kingdom
MH  - Vitamin D-Binding Protein/blood
PMC - PMC3161932
EDAT- 2011/07/16 06:00
MHDA- 2011/11/05 06:00
PMCR- 2011/07/14
CRDT- 2011/07/16 06:00
PHST- 2010/10/18 00:00 [received]
PHST- 2011/07/14 00:00 [accepted]
PHST- 2011/07/16 06:00 [entrez]
PHST- 2011/07/16 06:00 [pubmed]
PHST- 2011/11/05 06:00 [medline]
PHST- 2011/07/14 00:00 [pmc-release]
AID - 1471-2350-12-95 [pii]
AID - 10.1186/1471-2350-12-95 [doi]
PST - epublish
SO  - BMC Med Genet. 2011 Jul 14;12:95. doi: 10.1186/1471-2350-12-95.