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01.12.2012 | Original investigation | Ausgabe 1/2012 Open Access

Cardiovascular Diabetology 1/2012

Association between 9p21 genetic variants and mortality risk in a prospective cohort of patients with type 2 diabetes (ZODIAC-15)

Zeitschrift:
Cardiovascular Diabetology > Ausgabe 1/2012
Autoren:
Gijs WD Landman, Jana V van Vliet-Ostaptchouk, Nanne Kleefstra, Kornelis JJ van Hateren, Iefke Drion, Klaas H Groenier, Rijk OB Gans, Harold Snieder, Marten H Hofker, Henk JG Bilo
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​1475-2840-11-138) contains supplementary material, which is available to authorized users.
Gijs WD Landman, Jana V van Vliet-Ostaptchouk contributed equally to this work.

Competing interests

The authors state that they have no conflicts of interest.

Authors’ contributions

GWDL: researched data, contributed to discussion, drafted manuscript. JVvVO: carried out the molecular genetic studies, participated in the sequence alignment, contributed to discussion and the drafting of the manuscript. NK, KJJvH, ID, ROBG, CW, HS, MHH and HJGB: contributed to discussion, reviewed manuscript. KHG: researched data/ statistician, reviewed manuscript. All authors read and approved the final manuscript. Both GWDL and JVvVO contributed equally to this paper.

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.
Zusatzmaterial
Authors’ original file for figure 1
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Authors’ original file for figure 2
12933_2012_570_MOESM2_ESM.tiff
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