Allele symptoms and conditions

Researchers have been doing studies for many years regarding trying to determine the role of genetic factors in patients response to Singulair (Montelukast).

This study from Spain identified the following gene variations hypothesize to be related to leukotriene pathway response. Sixty one patients with asthma were studied. Three gene types were identified:

type 1. Thirty-two patients (52.5%) were homozygous for the five repeats allele;
type 2. 17 (27.9%) were heterozygous (4/5 repeats)
type 3. 12 (19.7%) were homozygous for 4/4 repeats.

The study showed that montelukast was effective for types 1 and 2 but not effective for type 3. Type 3 represented approximately 20% of the group study.

"After the montelukast treatment decrease number of asthma exacerbations, improvement of FEV(1) and decreased use of beta(2) agonists was observed in patients with 5/5 or 4/5 repeats. Conversely, the patients with 4/4 repeats genotype did not modify these data after treatment."

So it seems logical that if it can be identified that montelukast is not effective for certain gene type variations, then montelukast could cause adverse side effects in certain gene type variations.

It is interesting that 20% of this group does not respond positively to montelukast. That is the exact same number that even Merck says gets a headache from montelukast. Headache is the highest incidence of adverse side effects that has been reported. That comparison, however, is just a coincidence because it has not been studied and proven. Maybe.

Where are the studies that pertain to gene type variations and adverse side effects? You would think that somebody could do them.

Respir Med. 2008 Jun;102(6):857-61. Epub 2008 Mar 12. Links
ALOX5 promoter genotype and response to montelukast in moderate persistent asthma.Telleria JJ, Blanco-Quiros A, Varillas D, Armentia A, Fernandez-Carvajal I, Jesus Alonso M, Diez I.
Institute of Biology and Molecular Genetics (IBGM/CSIC), University of Valladolid, Valladolid, Spain. ******

BACKGROUND: It was hypothesized that asthmatic patients with mutant alleles in the leukotriene pathway should not respond to leukotriene receptor antagonists and the concept of a tailored treatment is increasingly supported. METHODS: Sixty-one patients (mean age 24.9 years, range 14-52) with moderate persistent asthma were clinical and immunological assess prior and after a 6-month treatment with montelukast. Tandem repeat polymorphisms were genotyped in the promoter (-147 to -176) of 5-lipoxygenase gene (ALOX5). RESULTS: Thirty-two patients (52.5%) were homozygous for the five repeats allele; 17 (27.9%) were heterozygous (4/5 repeats) and 12 (19.7%) were homozygous for 4/4 repeats. After the montelukast treatment decrease number of asthma exacerbations, improvement of FEV(1) and decreased use of beta(2) agonists was observed in patients with 5/5 or 4/5 repeats. Conversely, the patients with 4/4 repeats genotype did not modify these data after treatment. CONCLUSIONS: It was confirmed that ALOX5 promoter polymorphisms have a clear influence in montelukast response in atopic moderate persistent asthma patients. The genetic study could identify those patients most likely to respond to montelukast.

PMID: 18339529

Cholesterol Decline May Be Associated With Early Stages of Dementia

By Will Boggs, MD

NEW YORK (Reuters Health) Jan 19 - A decline in total cholesterol
levels precedes the diagnosis of dementia by at least 15 years,
according to an epidemiologic study reported in the January issue of
the Archives of Neurology.

"Studies like this are extremely valuable because they can provide a
'window' on to processes going on early in dementia, allowing
researchers to look back in time at people's health and other
characteristics and compare these between people who develop dementia
and those who do not," Dr. Robert Stewart from King's College London,
UK told Reuters Health.

Dr. Stewart and colleagues used data from the Honolulu-Asia Aging
Study to compare the natural history of cholesterol level change over
a 26-year period between 56 men who were found to have dementia at
examination 3 years after the last cholesterol measurement and 971 men
who did not have dementia.

Total cholesterol levels at the beginning of the study did not differ
by later dementia status, the authors report, but the decline in
subsequent cholesterol levels was significantly steeper among men who
went on to develop dementia.

Adjustment for potential confounding factors strengthened the
association between cholesterol level decline and the development of
dementia, the results indicate.

The cholesterol level decline was most marked in men with dementia and
the APOE epsilon-4 allele and in those with dementia and worse self-
reported general health at the final cholesterol measurement, the
researchers note.

"The observed associations may not represent direct causal pathways,"
the investigators say. "Hypocholesterolemia is recognized to be
associated with frailty and poor general health. It also has been
found to be specifically associated with inflammatory markers and poor
nutritional status."

Rather, they suggest, "It is possible that the decline in cholesterol
levels is a marker for early processes that reflect neurodegenerative
changes and also lead to a decline in general health status."

The drop in cholesterol was not a result of medication. "Very few of
the participants in this study were receiving cholesterol lowering
treatment at the time the decline in cholesterol levels was observed
(there were few cholesterol lowering medications around at that time
in the 1970s), so medication was not responsible for this," Dr.
Stewart explained.

"The drop in cholesterol was instead probably caused by some other
event and was a 'marker' of risk rather than actually increasing the
risk itself," he concluded.

Arch Neurol 2007;64:103-107.