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Association between 9p21 genetic variants and mortality risk in a prospective cohort of patients with type 2 diabetes (ZODIAC-15)
- Source :
- Cardiovascular Diabetology; Vol 11, Cardiovascular Diabetology, Vol 11, Iss 1, p 138 (2012), Cardiovascular Diabetology, 11:138. BioMed Central Ltd., Cardiovascular Diabetology
- Publication Year :
- 2012
- Publisher :
- Springer Science and Business Media LLC, 2012.
-
Abstract
- The genomic region at 9p21 chromosome near the CDKN2A/CDKN2B genes is associated with type 2 diabetes(T2D) and cardiovascular disease(CVD). The effect of the 9p21 locus on long-term mortality in patients with T2D has yet to be determined. We examined three single nucleotide polymorphisms (SNPs) on 9p21, consistently and independently associated with T2D (rs10811661) or CVD (rs10757278, rs2383206), in relation to the risk of total and cardiovascular mortality in diabetic patients. We also aimed to replicate the previously observed interaction between rs2383206 and glycemic control on mortality. Genotypes for three SNPs were determined in 914 individuals from a prospective cohort of T2D patients of Dutch origin. Associations with mortality were assessed using Cox proportional hazard analyses. After a median follow-up of 9.5 years, 358 out of 914 patients had died. The hazard ratio (HR) for total mortality among individuals homozygous for the T2D-risk allele of rs10811661 compared to non-homozygous individuals was 0.74(95%CI 0.59-0.93). For the carriers of both CVD-risk alleles of rs10757278, the HR for total mortality was 1.31(95%CI 1.01-1.70). We found a significant interaction between rs2383206 and HbA1c on mortality, which was higher among patients with two CVD-risk alleles in the two lowest HbA1c tertiles (HR 1.68(95%CI 1.08-2.63); HR 1.48(95%CI 1.01-2.18). In conclusion, common variants on 9p21 were associated with mortality in patients with T2D in a Dutch population. The T2D SNP was inversely associated with mortality, while the CVD SNP increased the risk for mortality. We confirmed a possible, although different, synergistic relationship between HbA1c and rs2383206 on total mortality.
- Subjects :
- Male
lcsh:Diseases of the circulatory (Cardiovascular) system
Time Factors
endocrine system diseases
Endocrinology, Diabetes and Metabolism
LOCI
Genome-wide association study
Disease
Type 2 diabetes
SUSCEPTIBILITY
030204 cardiovascular system & hematology
Linkage Disequilibrium
0302 clinical medicine
Gene Frequency
Risk Factors
Cause of Death
GLYCEMIC CONTROL
Prospective Studies
Prospective cohort study
Original Investigation
Netherlands
0303 health sciences
Homozygote
Middle Aged
CVD
PROSTATE-CANCER
Type 2 Diabetes
3. Good health
CHROMOSOME 9P21
Phenotype
9p21
Cardiovascular Diseases
SINGLE NUCLEOTIDE POLYMORPHISMS
CORONARY-ARTERY-DISEASE
Female
Chromosomes, Human, Pair 9
Cardiology and Cardiovascular Medicine
endocrine system
medicine.medical_specialty
SNP
Single-nucleotide polymorphism
Locus (genetics)
Polymorphism, Single Nucleotide
Risk Assessment
03 medical and health sciences
Internal medicine
Diabetes mellitus
Genetics
medicine
Humans
Genetic Predisposition to Disease
GENOME-WIDE ASSOCIATION
Mortality
Allele frequency
Aged
Proportional Hazards Models
030304 developmental biology
Glycated Hemoglobin
business.industry
nutritional and metabolic diseases
medicine.disease
Survival Analysis
Logistic Models
Diabetes Mellitus, Type 2
MYOCARDIAL-INFARCTION
ATHEROSCLEROSIS
lcsh:RC666-701
Multivariate Analysis
business
human activities
Biomarkers
Subjects
Details
- ISSN :
- 14752840
- Volume :
- 11
- Database :
- OpenAIRE
- Journal :
- Cardiovascular Diabetology
- Accession number :
- edsair.doi.dedup.....e418f08725539831ab4270036d63d2f6