Genetic variants, plasma lipoprotein(a) levels, and risk of cardiovascular morbidity and mortality among two prospective cohorts of type 2 diabetes.

TLDR: The data indicate that the effect of Lp(a) on CVD risk among diabetic patients might be different from that in the general population.

Abstract: Aims To examine the relations between genetic loci, plasma lipoprotein(a) [Lp(a)] levels, and cardiovascular disease (CVD) risk among diabetic patients and compare with the observations in the general population. Methods and results In two prospective cohorts of patients with type 2 diabetes ( n = 2308) from the Nurses' Health Study and the Health Professional Follow-Up Study, we performed (i) genome-wide association (GWA) scans for plasma Lp(a); (ii) prospective analysis of plasma Lp(a) for CVD risk and mortality; and (iii) genetic association analysis for CVD risk and mortality. Meta-analysis of the two GWA scans yielded 71 single-nucleotide polymorphisms (SNPs) on chromosome 6q associated with plasma Lp(a) levels at a genome-wide significance level ( P 0.09). For the best SNP rs10455872 for plasma Lp(a) levels, the OR for CHD, CVD, and CVD death was 0.94 (95% CI: 0.69–1.28), 0.97 (0.72–1.29), and 1.23 (0.79–1.92), respectively. The genetic effect on CHD risk showed a significant heterogeneity between the diabetic and the general populations ( P = 0.006). Conclusion Our data indicate that the effect of Lp(a) on CVD risk among diabetic patients might be different from that in the general population. Diabetes status may attenuate the relation between Lp(a) and cardiovascular risk.