Feng, Xiaodong_ Xie, Hong-Guang - Applying pharmacogenomics in therapeutics-CRC Press (2016)

Essential Pharmacogenomic Biomarkers in Clinical Practice
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and mucous membranes) and toxic epidermal necrolysis (a dermatologic disorder
characterized by symptoms such as widespread erythema and necrosis) that are
associated with significant mortality and morbidity. 101 The HLA-B*5801 allele was
shown to be strongly associated with allopurinol-induced ADRs in several Asian
and non-Asian populations. 102–106 HLA-B*5801 allele screening is currently recommended
to be considered in patients who will be treated with allopurinol. 107
PHARMACOGENOMIC BIOMARKERS UNDER DEVELOPMENT
Although significant progress has been made in detecting clinically implementable
pharmacogenomic biomarkers, there still remain grand challenges to optimize precision
and personalized medicine for patients with various diseases and disorders,
given the complex nature of pathogenesis and drug response. With the advances
in high-throughput profiling technologies, particularly those based on the nextgeneration
sequencing (NGS), numerous trials and studies are ongoing with the ultimate
goals of detecting more sensitive and specific biomarkers of drug response
phenotypes. Some of these biomarkers under development are introduced with a
focus on novel biomarkers beyond traditional drug-metabolizing genes for certain
common, complex diseases (Table 3.2).
Cardiovascular Diseases
Besides these well-established CYP genes, previous studies on cardiovascular diseases,
especially recent genome-wide scans enabled by the advanced high- throughput
profiling technologies, have implicated several strong candidate genes that may be
responsible for the interindividual variation in drug response phenotypes. Of particular
interest are genes that may determine therapeutic responses to statin treatments,
given that statins are widely used to reduce the risk of major cardiovascular
events. Among the top candidate genes for statin response are ABCB1 (encoding
ATP-binding cassette, subfamily B, member 1), CETP (encoding cholesterol ester
transfer protein), HMGCR (encoding 3-hydroxy-3-methylglutaryl-coA reductase), and
TABLE 3.2
Some Novel Pharmacogenomic Biomarkers under Development
Disorder Drug Biomarker Host Gene
Cardiovascular diseases Statins rs1128503, rs2032582, ABCB1
rs1045642 108
rs5883, rs9930761 109
CETP
rs5908, rs12916 110
HMGCR
rs4149056 111
SLCO1B1
Chronic myeloid leukemia Imatinib, nilotinib Philadelphia chromosome 113–115 BCR-ABL
Acute myeloid leukemia Ruxolitinib V617F 117 JAK2
Obsessive–compulsive disorder Selective serotonin rs17162912 118
DISP1
reuptake inhibitors rs9957281 118
DLGAP1