Biology Reference
In-Depth Information
PER2 participates in modulating alcohol consumption, similar to its
counterpart PER1. A SNP located in intron 3 of PER2 , 10,870 A/G, is asso-
ciated with the quantity of alcohol intake. 85,86 This SNP resides in a CAT-
TTTmotif, which is conserved in human, chimpanzee, and rat. 85 It is also in
an enhancer-like structure, which contains several transcriptional factor-
binding site motifs. This SNP alters the binding motifs for Sp1, c-myb,
and NF- k B, possibly resulting in altered transactivation of PER2 .m Per2
mutant mice exhibit increased alcohol consumption, accompanied by
enhanced glutamate levels in the extracellular space in the brain. This is
believed to be a result of reduced expression of the glutamate transporter
gene, Eaat1 , and thus reduced uptake of glutamate by astrocytes.
Acamprosate, a drug used to prevent craving and relapse in alcoholic
patients, reduced the enhanced glutamate levels and normalized the
increased alcohol intake in m Per2 mutant mice. Collectively, these data sug-
gest that PER2 acts to suppress glutamatergic signaling, which in turn influ-
ences alcohol drinking. Besides being involved in modulating alcohol
consumption, the PER2 10870 A/G SNP is also associated with SAD. 24
PER2 is linked to the risk of cancer. An intronic SNP in PER2 is signif-
icantly associated with susceptibility to prostate cancer, 23 whereas the afore-
mentioned 1244 Gly/Glu associated with morningness and depression
vulnerability also correlates with the risk of breast cancer in combination
with an SNP in CLOCK . 59
7. PER3
Several polymorphisms in PER3 have been suggested to contribute to
determination of diurnal preference and DSP. 63,87-91 The most well-studied
polymorphism among these is a polymorphic repeat region with four or five
copies of a 54-bp repetitive sequence (4-repeat vs. 5-repeat) in exon 18.
However, this association with morningness/eveningness attenuates with
age. 90,92 Human subjects homozygous for the long allele are particularly sen-
sitive to blue-enriched light, as such light significantly suppresses evening
rise of endogenous melatonin in homozygotes for the long allele but not
the short allele. 93 Likewise, individuals homozygous for the long allele
exhibit more pronounced response to the alerting effects of light compared
to homozygotes for the short allele. Waking electroencephalographic (EEG)
activity in the theta range (5-7 Hz), which is a putative correlate of sleep-
iness, is substantially attenuated during exposure to blue-enriched light in
subjects homozygous for the long allele but not the short allele. This length
Search WWH ::




Custom Search