OS 30-05 GENETIC RISK SCORE DETERMINES DIPPING PROFILE IN PATIENTS WITH CORONARY HEART DISEASE

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Abstract

Objective:

The aim of this study is to report the relationship between certain single nucleotide polymorphisms (SNP) and blunted nighttime blood pressure (BP) fall in hypertensive patients with CAD confirmed by coronary angiography.

Design and Method:

According to the percentage decrease in mean systolic (SBP) and diastolic BP (DBP) during the nighttime period subjects were classified as dippers or non-dippers (nighttime relative SBP or DBP decline ≥ and <10% respectively). SNPs were selected from genome-wide association studies in which genome-wide association exceeded threshold of p < 5 × 10–8. The SNPs were genotyped using IPLEX reaction on a MassARRAY platform. As a quality control, we re-genotyped a random sample of 20% of the successfully genotyped samples for all genotypes, and the concordance was 99.9%.

Design and Method:

Genetic Risk Score (GRS18) was constructed to evaluate additive effect of 18 SNPs for non-dipping status. This multilocus score was created by summing the number of risk allels (0/1/2) for each of the 18 SNPs (1 and 2 for heterozygous and homozygous risk allele, respectively and 0 for homozygous non-risk allele).

Results:

In the present study, 1345 subjects with CHD were included. During follow-up period (median 8.3 years, interquartile range 5.3 to 9.0 years) there were 245 all-cause deaths (18.2%) including 114 CV deaths (8.5%). There were significant differences in the number of revascularizations between non-dippers SBP and DBP and dippers SBP and DBP (48.0% vs. 36.4%, p < 0.01). SNPs of the genes: MIA3, MRAS, PCSK9, SMG6, ZC3HC1 were related to a higher risk of non-dipping SBP and DBP status. The association between GRS18 and non-dipping status is presented in Table.

Conclusions:

In the present study, polymorphisms of genes related to CHD (MIA3, MRAS, PCSK9, SMG6, and ZC3HC1) were associated with non-dipping SBP and DBP profile and GRS18 was associated with non-dipping status. In addition, this profile was related to a higher risk of revascularization.

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