parking, don't know if this is still in effect, from S-1, filed 3/29/2000...... also don't have **ANY** understanding of utility, although the gene and gene product are of obvious interest........ merely parking!......
In the diagnostics/laboratory sector, we market the ApoE genotype through a
July 1999 co-marketing agreement with Nova Molecular, Inc., a clinical
laboratory services company in which we have an equity interest. The ApoE
genotype is associated with Alzheimer's and certain cardiovascular diseases.
ApoE is the most widely cited pharmacogenomic marker in the industry. Under this
agreement, we will earn royalties on ApoE genotyping tests sold by us and
performed by Nova Molecular. Our agreement with Nova Molecular is for a
three-year term and may be automatically renewed for additional terms of one
year each, unless either party gives notice to the other of its intent not to
renew at least 90 days prior to the expiration of each term.
Hum Genet 1999 Feb;104(2):158-63
Further evidence for a synergistic association between APOE epsilon4 and
BCHE-K in confirmed Alzheimer's disease.
Wiebusch H, Poirier J, Sevigny P, Schappert K.
Nova Molecular Inc., Montreal (PQ), Canada. wiebusch@nmidepth.com
Recent reports on a potential association between the K-variant of the gene for
butyrylcholinesterase (BCHE-K) and Alzheimer's disease (AD) are discordant. An initial finding
of association through a synergistic enhancement of risk of APOE epsilon4 with late-onset AD
has not been confirmed by others. We have conducted a case-control study of
histopathologically confirmed AD (n=135) and non-AD (n=70) cases (age of death > or =60
years), in which we have genotyped for APOE epsilon4, BCHE-K, and BCHE-A1914G, a
silent polymorphism 299 bp downstream of the BCHE-K mutation. The allelic frequency of
BCHE-K was 0.13 in the controls and 0.23 in the AD cases, giving a carrier odds ratio (OR(c))
of 2.1 (95% C.I. 1.1-4.1) for BCHE-K in confirmed AD. The allelic frequency for the
BCHE-1914G variant was 0.19 and 0.33 in controls and AD cases, respectively (OR(c)=2.4;
95% C.I. 1.3-4.5). In an older sub-sample of 27/70 controls and 89/135 AD patients with ages
of death > or =75 years, the OR(c) was increased to 4.5 (95% C.I. 1.4-15) for BCHE-K and
2.7 (95% C.I. 1.0-7.2) for BCHE-1914G carriers. The BCHE-K association with AD became
even stronger in carriers of at least one APOE epsilon4 allele. Only three out of 19 controls
compared with 39/81 AD cases carried BCHE-K in addition to APOE epsilon4, giving an odds
ratio of confirmed AD of 5.0 (95% C.I. 1.3-19) for BCHE-K carriers within APOE epsilon4
carriers. Five out of 19 controls and 52/81 AD cases carried BCHE-1914G, giving the same
odds ratio of confirmed AD of 5.0 (95% C.I. 1.6-16) for BCHE-1914G carriers within APOE
epsilon4 carriers. In addition, our results suggest strong linkage disequilibrium between BCHE-K
and BCHE-1914G but no major association of the sole BCHE-1914G chromosome with AD.
We conclude that BCHE through its K-variant, rather than a nearby marker, is a susceptibility
factor for AD and enhances the AD risk defined by APOE epsilon4 alone in an age-dependent
manner. |
