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

252 Applying Pharmacogenomics in Therapeutics
Case Report
Twins born at 36 weeks’ gestation were treated with vitamin D (400 IU from fortified
milk formula + 1500 IU supplementation because of prematurity). One presented
with vomiting and failure to thrive at six months of age. He had severe hypercalcemia
(3.68 mmol/L; normal value: < 2.6) with low PTH serum level (1 ng/L, normal value:
10–55), slightly elevated serum level of 25(OH)D at 140 nmol/L, normal serum
level of 1,25(OH)2D at 96 pmol/L (normal value: 60–120), and hypercalciuria (Ca/
creatinine ratio: 4.3) associated with nephrocalcinosis. Normalization of calcemia
was observed within three weeks after switching from milk to an infant formula
containing low calcium and no vitamin D content (Locasol; Nutricia-France, SA,
St. Ouen, France). Vitamin D supplement was withdrawn together with appropriate
hydration and furosemide therapy. Later, the child tolerated vitamin D fortified milk
at 600 IU/d with normal serum levels of 25(OH)D. However, the summer serum level
of 1,25(OH)2D subsequently rose to 360 pmol/L, despite sun protection. Polymerase
chain reaction (PCR) amplification of exons 1–11 of CYP24A1 was performed in
this twin showing no PCR product for exons 9 and 11. This was later confirmed
by quantitative PCR using specific TaqMan (Assays Life Technologies, St. Aubin,
France) probes for intron 8 and 10, respectively. The deletion was shown to be inherited
from heterozygous nonconsanguineous parents who displayed only one allele
for intron 10.
The patient is now 18 years old, and his nephrocalcinosis appears unchanged on
ultrasound examination. During the summer months, his calcium levels still rise to
the upper limit of normal but with elevated serum levels of 1,25(OH)2D and low
PTH levels. His unaffected twin, who received the same high amount of vitamin D
per day did not exhibit IIH and did not have the CYP24A1 mutation. 18
Selenium
Selenium has antioxidative activity, which protects the human body from free radicals
and carcinogens. Selenium may also relieve inflammation, enhance immunity
to fight against infections, promote heart health, and enhance the role of vitamin E.
Selenium is essential for the male reproductive system and metabolism. Selenium
intake deficiency may be associated with cancer, premature aging, cataracts, hypertension,
recurrent infections, and so on.
Alzheimer disease (AD) is a complex genetic disease, characterized by a variety
of cognitive disorders. Oxidative stress may play a key role in its pathogenesis.
Cytosolic glutathione peroxidase (GPx1) widely exists in many tissues that have high
oxidative stress. The GPx1 gene Pro198Leu can lead to reduced enzyme activity.
In one research involving elderly AD patients and healthy controls, researchers have
found that GPx1 Pro198Leu polymorphism itself was not associated with the pathogenesis
of AD. However, the selenium levels in the plasma and erythrocyte of the
AD patients homozygous for the Pro198Pro were significantly lower than that in
healthy subjects homozygous for the Pro198Pro (31.44 vs. 54.87 μg/L, p = 0.002;
40.25 vs. 87.75 μg/L, p = 0.0004), the selenium levels in erythrocytes were positively
correlated with GPx1 activity in AD patients and healthy controls, both of which