PMID- 19077211
OWN - NLM
STAT- MEDLINE
DCOM- 20091113
LR  - 20211020
IS  - 1471-2261 (Electronic)
IS  - 1471-2261 (Linking)
VI  - 8
DP  - 2008 Dec 10
TI  - The Asp298 allele of endothelial nitric oxide synthase is a risk factor for 
      myocardial infarction among patients with type 2 diabetes mellitus.
PG  - 36
LID - 10.1186/1471-2261-8-36 [doi]
AB  - BACKGROUND: Endothelial dysfunction plays a central role in atherosclerotic 
      progression and cardiovascular complications of type 2 diabetes mellitus (T2DM). 
      Given the role of nitric oxide in the vascular system, we aimed to test 
      hypotheses of synergy between the common endothelial nitric oxide synthase (eNOS) 
      Asp298 allele and T2DM in predisposing to acute myocardial infarction (AMI). 
      METHODS: In a population-based patient survey with 403 persons with T2DM and 799 
      healthy subjects from the population without diabetes or hypertension, we 
      analysed the relation between T2DM, sex and the eNOS Asp298 allele versus the 
      risk for AMI. RESULTS: In an overall analysis, T2DM was a significant independent 
      risk factor for AMI. In patients with T2DM, homozygosity for the eNOS Asp298 
      allele was a significant risk factor (HR 3.12 [1.49-6.56], p = 0.003), but not in 
      subjects without diabetes or hypertension. Compared to wild-type non-diabetic 
      subjects, all patients with T2DM had a significantly increased risk of AMI 
      regardless of genotype. This risk was however markedly higher in patients with 
      T2DM homozygous for the Asp298 allele (HR 7.20 [3.01-17.20], p < 0.001), 
      independent of sex, BMI, systolic blood pressure, serum triglycerides, HDL 
      -cholesterol, current smoking, and leisure time physical activity. The pattern 
      seemed stronger in women than in men. CONCLUSION: We show here a strong 
      independent association between eNOS genotype and AMI in patients with T2DM. This 
      suggests a synergistic effect of the eNOS Asp298 allele and diabetes, and 
      confirms the role of eNOS as an important pathological bottleneck for 
      cardiovascular disease in patients with T2DM.
FAU - Odeberg, Jacob
AU  - Odeberg J
AD  - Department of Medicine, Atherosclerosis Research Unit, Centre for Molecular 
      Medicine, Karolinska Institutet, University Hospital, Stockholm, Sweden. 
      jacob.odeberg@ki.se
FAU - Larsson, Charlotte A
AU  - Larsson CA
FAU - Rastam, Lennart
AU  - Rastam L
FAU - Lindblad, Ulf
AU  - Lindblad U
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20081210
PL  - England
TA  - BMC Cardiovasc Disord
JT  - BMC cardiovascular disorders
JID - 100968539
RN  - 30KYC7MIAI (Aspartic Acid)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type III)
SB  - IM
MH  - *Alleles
MH  - Aspartic Acid/*genetics
MH  - Data Collection
MH  - Diabetes Mellitus, Type 2/*enzymology/*genetics/pathology
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Myocardial Infarction/*enzymology/*genetics/pathology
MH  - Nitric Oxide Synthase Type III/*genetics
MH  - Risk Factors
PMC - PMC2636751
EDAT- 2008/12/17 09:00
MHDA- 2009/11/17 06:00
PMCR- 2008/12/10
CRDT- 2008/12/17 09:00
PHST- 2008/06/15 00:00 [received]
PHST- 2008/12/10 00:00 [accepted]
PHST- 2008/12/17 09:00 [entrez]
PHST- 2008/12/17 09:00 [pubmed]
PHST- 2009/11/17 06:00 [medline]
PHST- 2008/12/10 00:00 [pmc-release]
AID - 1471-2261-8-36 [pii]
AID - 10.1186/1471-2261-8-36 [doi]
PST - epublish
SO  - BMC Cardiovasc Disord. 2008 Dec 10;8:36. doi: 10.1186/1471-2261-8-36.