Title The prevalence of rare variants potentially important for the response to medicines used for CVD treatment in the Lithuanian population /
Authors Pranculis, Aidas ; Rančelis, Tautvydas ; Ambrozaitytė, Laima ; Uktverytė, Ingrida ; Domarkienė, Ingrida ; Burokienė, Neringa ; Kučinskienė, Zita Aušrelė ; Kučinskas, Vaidutis
DOI 10.4172/2153-0645.1000157
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Is Part of Journal of pharmacogenomics & pharmacoproteomics.. Los Angeles : Omics Publishing Group. 2016, Vol. 7, no 2, art. no 1000157 [p. 1-6].. ISSN 2153-0645
Keywords [eng] Indels ; Coronary heart disease ; ANNOVAR ; CVD treatment
Abstract [eng] Cardiovascular disease (CVD) is one of the leading causes of death among Europeans and around the world. Major factors that are considered relevant for the efficacy or adverse drug reactions (ADRs) caused by drugs used for CVD treatment have been identified through GWAS studies mostly using low density common variant genotyping arrays. In this study whole exome sequencing (WES) was carried out to identify genomic variants relevant for CVD treatment. The study group included 98 (49 males and 49 females) self-reported healthy unrelated individuals from the Lithuanian population with at least three generations of Lithuanian ethnicity and residency in the same ethnolinguistic region. After performing WES genetic loci of 55 genes that were reported as relevant to the efficacy or ADRs caused by drugs used for CVD treatment were analyzed using LifeScopeTM and ANNOVAR software. The analysis of small indels in the selected regions revealed 13 exonic frameshift indels and a single intronic splice site variant that may affect the efficacy or cause ADRs in patients treated for CVD. Over 400 potentially relevant SNVs in different frequencies were detected in the genes reported to be important for CVD treatment. The strength of evidence analysis identified 14 SNVs most likely to be relevant for CVD treatment. The frequency distribution of several variant alleles that have been shown to be highly important for CVD treatment in the CYP2D6 (rs16947) and ADRB1 (rs1801253) as well as several variants in the CYP2C9 and NAT2 genes were determined to be significantly (p<0.05) different from other Caucasian populations showing the potential benefit of pharmacogenomic testing prior to treatment in the Lithuanian population. The research was carried out under the LITGEN project. LITGEN project (VP1-3.1-ŠMM-07-K-01-013) was funded by the European Social Fund under the Global Grant measure.
Published Los Angeles : Omics Publishing Group
Type Journal article
Language Lithuanian
Publication date 2016