Dear Editor,
Genetic variants associated with warfarin dosage in Kuwaiti
population
A
recent study by Sivadas and colleagues published in the current issue reported
the genetic variants linked to the dosage levels of warfarin and clopidogrel in
Qatari population, by conducting comprehensive pharmacogenetic mapping of exomic
variants. In this connection, we would like to draw your attention towards our
observations (Alsmadi et al. 2014) on the prevalence of warfarin drug response
associated variant, rs2108622_C>T, in Kuwaiti individuals scrutinizing 13
exomes and three whole genomes (two Saudi Arabian tribe and one Persian,
ancestries). With reference to an earlier study that showed poor response to the
administered warfarin dose, we detected rs2108622_C>T to be the prime
genetic determinant of warfarin dose in Kuwaiti population. Further to
substantiate this, we augmented our previous analysis with a total of 125
exomes of Kuwaiti individuals and intend to present the outcomes through this
letter. We strongly hope that this addition would benefit the worldwide understanding
of population-specific drug dosage especially in the Arab region.
We
scrutinized exomes of 125 Kuwaiti individuals, belonging to subgroups of
inferred ancestries - Saudi Arabian tribe (KWS-50), Persian (KWP-51) and
Bedouin with African genetic component (KWB-24) for the pharmacogenetics
variants associated with drug response. As a result, we discerned four out of
six variants reported by Sivadas et al. (2016). Among those four variants, T
allele frequency at rs2108622 of CYP4F2 remained significant with an overall frequency of 42%. When compared with the continental
population groups, Kuwaitis (42%) are more similar to South Asians (41%) in
their rs2108622_T frequency.
Further,
examining subpopulation-wise occurrence of the variants we found KWS carrying significant
number (50%) of T allele whereas KWP and KWB carry 38% and 35%, respectively. Subsequent
genotype level analyses revealed that KWS individuals possess 26% of risk
genotype rs2108622_TT, which requires high dose of warfarin, while KWP and KWB correspondingly
hold 16% and 8%. Notably, this scenario is close to Bedouins of Qatar (Q-BED)
carrying 30% rs2108622_TT. Here, it’s worth stating that Qatari subpopulation Q-BED
was classified based on the Arabian genetic component as in HGDP whereas for
Kuwaitis we stratified the same as Saudi Arabian tribe (KWS) and also Kuwaiti
Bedouins with African component as Bedouins (KWB). This is evident from the less
occurrence of the risk genotype rs2108622_TT in KWB (8%) and Q-AFR (4%). In
addition we also noted that rs7900194_G>A variant is observed only in KWB with
2% and not in KWS and KWP. Overall, our observations indicate the uniform
prevalence of pharmacogenetic variants among the population subgroups of the Arab
region and warrants the need of formulating Arabian-specific warfarin dosage
kits.