PHARMACOGENETIC PROFILE OF CYP2D6 GENE IN CROATIAN ROMA

doctoral thesis

• Title (english): FARMAKOGENETSKI PROFIL GENA CYP2D6 ROMA U HRVATSKOJ
• Author: Anita Stojanović Marković
• Mentor: Marijana Peričić Salihović (mentor)
• Committee member: Petra Korać (predsjednik povjerenstva)
• Committee member: Ana Galov (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2023, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology
• Universal decimal classification (UDC): 577 - Biochemistry. Molecular biology. Biophysics

Abstract

The CYP2D6 gene encodes the homonymous enzyme responsible for the metabolism of about
25% of clinically prescribed drugs, although it accounts for only 2% of all cytochromes in the
human liver. The Roma are an example of a founder population where centuries of isolation
and migrations have left their mark on the gene pool. Results of this study showed the
influence of demographic history on single nucleotide polymorphisms in three socioculturally different studied Roma populations. Their South Asian origin is seen in the
frequencies of polymorphic variants, as well as the increased frequency of star alleles *10 and
*41. Phenotypically, normal metabolizers are the most common among Roma (51.6-65.1%),
while slow metabolizers are the least common (0-7.4%). The similarity of the Roma
population to European and Asian populations is evident from the LD pattern of the CYP2D6
gene region. The three Roma groups differ significantly (p<0.0001) in the distribution of the
five most represented haplotypes (*1, *2, *4, *10, *41), which confirms the need to
investigate them as separate groups for more accurate prescription of drugs that are
metabolized by CYP2D6.

Abstract (english)

Gen CYP2D6 kodira za istoimeni enzim odgovaran za metabolizam oko 25% klinički
propisanih lijekova iako čini samo 2% svih citokroma u jetri čovjeka. Romi su primjer
populacije utemeljitelja u kojoj su višestoljetna izolacija i migracije ostavile traga u njihovih
zalihi gena. Rezultati ovog istraživanja su pokazali utjecaj demografske povijesti na varijacije
polimorfizma jednog nukleotida u tri socio-kulturno različite, istraživane romske populacije.
Njihovo južnoazijsko porijeklo očituje se u frekvencijama polimorfnih varijanti, kao i
povećanoj frekvenciji zvjezdastih alela *10 i *41. Fenotipski gledano, kod Roma je
najučestaliji normalni metabolizator (51,6-65,1%), dok je spori najmanje zastupljen (0-7,4%).
Sličnost Roma europskim i azijskim populacijama vidljiva je iz obrasca LD-a genske regije
CYP2D6. Tri romske skupine se značajno razlikuju (p<0,0001) u distribuciji pet
najzastupljenijih haplotipova (*1, *2, *4, *10, *41), što potvrđuje potrebu da se u
istraživanjima proučavaju kao zasebne grupe radi točnijeg propisivanja lijekova koje
metabolizira CYP2D6.

• Keywords: CYP2D6 gene; Roma population; ADME genes; pharmacogenetics; personalized medicine; single nucleotide polymorphism; haplotype
• Keywords (english): CYP2D6; Romske populacije; geni ADME; farmakogenetika; personalizirana medicina; polimorfizam jednog nukleotida; haplotip
• Language: english
• URN:NBN: urn:nbn:hr:217:424038
• Promotion: 2023
• Study programme: Title: Biology; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti, područje prirodnih znanosti, polje biologija (doktor/doktorica znanosti, područje prirodnih znanosti, polje biologija)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2023-02-28 13:45:47