Introduction: Two regulatory polymorphisms (rs1040079 and rs9356058) shared by PARK2 and PACRG
genes were identified as major risk variants for leprosy susceptibility. The aim of this study was to
investigate if allele frequencies of these polymorphisms in the isolated population of the island of Mljet,
which served as a quarantine for leprosy patients during past centuries, were different to allele
frequencies in two control populations with no history of leprosy.
Subjects and methods: This study included 88 unrelated Caucasian individuals from the island of Mljet
while two control groups included 93 individuals from the island of Rab and 160 individuals from the
region of Split. Genotyping for rs1040079 and rs9356058 was performed by “real-time” PCR analysis. We
also compared the allele frequency of the rs9356058 polymorphism from the population of Mljet with
allele frequencies derived from the existing genome wide association scans in two additional island
populations, Vis (924 subjects) and Korcula (909 subjects).
Results: We found a significant increase in the frequency of rs9356058 allele C in the population of Mljet
when compared to both control groups. We also observed a significant increase in the frequency of
rs1040079 allele A in the population of Mljet when compared with the population of Rab, however this
increase was not significant when compared with the population of Split. Allele frequencies of both
examined polymorphisms did not differ between the two control populations. Protective haplotype
rs9356058-rs1040079 CA was also more frequent in the population of Mljet compared with the Rab and
Split populations. In addition, an increase of frequency of rs9356058 allele C was also observed in the
population of Mljet when compared with the frequency in the Korcula population.
Conclusion: The results of our study show the association of polymorphisms rs9356058 and rs1040079 in
gene PARK2/PACRG with leprosy. The results of our study indicate that exposure to leprosy and mortality
in the population caused by leprosy on Mljet resulted in the selection of rs9356058 “protective” C allele
in the PARK2 gene, while this was not observed in the two control groups. This is the first study to assess
the genetic susceptibility to leprosy in a European population