Original scientific paper
https://doi.org/10.3325/cmj.2022.63.117
Pharmacogenetic distinction of the Croatian population from the European average
Željka Celinšćak
; Institute for Anthropological Research, Zagreb, Croatia
Matea Zajc Petranović
; Institute for Anthropological Research, Zagreb, Croatia
Maja Šetinc
; Institute for Anthropological Research, Zagreb, Croatia
Anita Stojanović Marković
; Institute for Anthropological Research, Zagreb, Croatia
Marijana Peričić Salihović
; Institute for Anthropological Research, Zagreb, Croatia
Hrvojka Marija Zeljko
; Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
Branka Janićijević
; Institute for Anthropological Research, Zagreb, Croatia
Nina Smolej Narančić
; Institute for Anthropological Research, Zagreb, Croatia
Tatjana Škarić Jurić
; Institute for Anthropological Research, Zagreb, Croatia
Abstract
Aim To compare the Croatian and European population in
terms of allele frequencies of clinically relevant polymorphisms in drug absorption, distribution, metabolism, and
excretion (ADME) genes.
Methods In 429 Croatian participants, we genotyped 27
loci in 20 ADME genes. The obtained frequencies were
merged with the published frequencies for the Croatian
population by sample size weighting. The study sample
obtained in this way was compared with the average data
for the European population from the gnomAD database.
Results Variant allele frequencies in the Croatian population
were higher in three and lower in two polymorphisms (Benjamini-Hochberg-corrected P values: 0.0027 for CYP2B6*4
rs2279343, CYP2C9*2 rs1799853, and VKORC1 rs9923231;
0.0297 for GSTP1 rs1695; 0.0455 for CYP2A6 rs1801272)
compared with the European population. The most marked
difference was observed for CYP2B6*4 (9.3% in Europe vs
24.3% in Croatia). The most clinically relevant findings were
higher variant allele frequencies in two polymorphisms related to lower warfarin requirements: VKORC1*2 (34.9% in
Europe vs 40.1% in Croatia) and CYP2C9*2 (12.3% in Europe
vs 14.7% in Croatia). This indicates that three-quarters of
Croatian people have at least one variant allele at these loci.
Variants in genes GSTP1 and CYP2A6 were significantly less
frequently observed in Croatia.
Conclusions Croatian population has a higher bleeding
and over-anticoagulation risk, which is why we recommend the prescription of lower doses of anticoagulation
drugs such as warfarin and acenocoumarol. Lower phenytoin, and higher bupropion and efavirenz doses are also
recommended in the Croatian population.
Keywords
Hrčak ID:
279007
URI
Publication date:
21.4.2022.
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