PMID- 17906106
OWN - NLM
STAT- MEDLINE
DCOM- 20080107
LR  - 20200930
IS  - 0363-6135 (Print)
IS  - 0363-6135 (Linking)
VI  - 293
IP  - 5
DP  - 2007 Nov
TI  - Atherogenic vascular and lipid phenotypes in young patients with Type 1 diabetes 
      are associated with diabetes high-risk HLA genotype.
PG  - H3175-9
AB  - Expression of human leukocyte antigen (HLA) class II molecules on islet 
      endothelial cells is a central vascular event in the pathogenesis of Type 1 
      diabetes. Previous studies demonstrated the ability of other vascular endothelial 
      cells to express HLA and thereby to process islet autoantigens on their surface. 
      We investigated whether the HLA-DQ2/8 genotype, which confers the highest risk 
      for Type 1 diabetes, is associated with early atherosclerosis in youths with this 
      disease. Brachial artery endothelium-dependent, flow-mediated dilation (BA-FMD) 
      and carotid artery intima-media thickness (CA-IMT), as well as markers of 
      systemic inflammation [C-reactive protein (CRP), fibrinogen, and orosomucoid], 
      HbA(1C), LDL, HDL, and total cholesterol, were assessed in 86 children and 
      adolescents with Type 1 diabetes (mean age and diabetes duration, 15 and 7 yr, 
      respectively) between 2004 and 2006. HLA genotypes were determined in dried blood 
      spots by an oligoblot hybridization method. As a result, HLA-DQ2/8 was detected 
      in 34 patients (DQ2/8). When this group was compared with the remaining patients 
      (non-DQ2/8, n = 52), there were no differences in age, diabetes duration, 
      HbA(1C), body mass index, inflammatory markers, and IMT (P > or = 0.4). In the 
      DQ2/8 group, LDL-to-HDL ratio was elevated compared with that in the non-DQ2/8 
      group (1.8 vs. 1.3, respectively; P = 0.001), whereas FMD did not significantly 
      differ between the groups (5.3% vs. 6.7%, respectively; P = 0.08). When patients 
      were further categorized in relation to CRP (cut-off value, 1 mg/l), BA-FMD was 
      significantly lower (3%, P < 0.01), whereas LDL-to-HDL ratio increased further 
      (2.2, P < 0.001) in the subgroup of DQ2/8 and CRP > or = 1 patients compared with 
      the remaining three subgroups. These associations remained significant after 
      adjustment for age, diabetes duration, and HbA(1C) by analysis of covariance. The 
      brachial artery responses to nitroglycerine were similar in all subgroups. In 
      conclusion, the diabetes-predisposing HLA-DQ2/8 genotype in children and 
      adolescents with Type 1 diabetes interferes with endothelial and lipid-related 
      mechanisms of early atherosclerosis, possibly in part through inflammatory 
      pathways.
FAU - Odermarsky, Michal
AU  - Odermarsky M
AD  - Pediatric Cardiology, Lund University Hospital, Lund, Sweden.
FAU - Nilsson, Anita
AU  - Nilsson A
FAU - Lernmark, Ake
AU  - Lernmark A
FAU - Sjoblad, Sture
AU  - Sjoblad S
FAU - Liuba, Petru
AU  - Liuba P
LA  - eng
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20070928
PL  - United States
TA  - Am J Physiol Heart Circ Physiol
JT  - American journal of physiology. Heart and circulatory physiology
JID - 100901228
RN  - 0 (HLA Antigens)
RN  - 0 (Lipids)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Atherosclerosis/*blood/epidemiology/*genetics
MH  - Child
MH  - Diabetes Mellitus, Type 1/*blood/epidemiology/*genetics
MH  - Diabetic Angiopathies/*blood/epidemiology/*genetics
MH  - Female
MH  - Genetic Predisposition to Disease/epidemiology/genetics
MH  - HLA Antigens/*genetics
MH  - Humans
MH  - Lipids/*blood
MH  - Male
MH  - Middle Aged
MH  - Phenotype
MH  - Prevalence
MH  - Risk Assessment/methods
MH  - Risk Factors
MH  - Sweden/epidemiology
EDAT- 2007/10/02 09:00
MHDA- 2008/01/08 09:00
CRDT- 2007/10/02 09:00
PHST- 2007/10/02 09:00 [pubmed]
PHST- 2008/01/08 09:00 [medline]
PHST- 2007/10/02 09:00 [entrez]
AID - 00795.2007 [pii]
AID - 10.1152/ajpheart.00795.2007 [doi]
PST - ppublish
SO  - Am J Physiol Heart Circ Physiol. 2007 Nov;293(5):H3175-9. doi: 
      10.1152/ajpheart.00795.2007. Epub 2007 Sep 28.