Association of Fatigue With Tryptophan Hydroxylase Genetic Polymorphisms in Women With IBS

[Murph]

Biol Res Nurs. 2018 Oct 11:1099800418806055. doi: 10.1177/1099800418806055. [Epub ahead of print]
Association of Fatigue With TPH2 Genetic Polymorphisms in Women With Irritable Bowel Syndrome.
Han CJ1, Jarrett ME2, Cain KC3, Jun S4, Heitkemper MM2.
Author information
1
1 Department of Public Health, University of Washington & Fred Hutchinson Cancer Research Center, Biobehavioral Cancer Prevention and Control Training Program, Seattle, WA.
2
2 Department of Biobehavioral Nursing and Health Informatics, University of Washington, Seattle, WA, USA.
3
3 Department of Biostatistics and Office of Nursing Research, University of Washington, Seattle, WA, USA.
4
4 College of Nursing, Keimyung University, Daegu, South Korea.
Abstract
Fatigue is the most common extraintestinal symptom in women with irritable bowel syndrome (IBS). Genetic polymorphisms of monoamines are associated with fatigue in many chronic diseases. In this pilot exploratory study, the primary aim was to determine whether genetic polymorphisms of tryptophan hydroxylase ( TPH1/TPH2), serotonin reuptake transporter ( SERT), or catechol-O-methyltransferase ( COMT) are associated with fatigue in women with IBS. Additionally, analysis explored whether these genetic associations with fatigue would be present when controlling for abdominal pain, psychological distress, feeling stressed, and sleepiness during the day. Secondary analysis of two randomized controlled trial baseline data sets in Caucasian women with IBS ( N = 185) was conducted. Participants kept a daily diary with one dimension (i.e., severity) for each of the 26 symptoms, including fatigue, for 28 days prior to randomization. DNA samples were tested for single-nucleotide polymorphisms (SNPs) of TPH1 (four SNPs) /TPH2 (one SNP), SERT (one SNP), and COMT (one SNP). Analysis of covariance was used to examine associations of percentage of diary days with moderate to very severe symptoms with genetic polymorphisms. Only one SNP, TPH2 rs4570625, was significantly associated with fatigue ( p = .005). T-allele (low functional) carriers of TPH2 (i.e., G/T or T/T genotypes) reported a greater percentage of days with moderate to very severe fatigue than G/G homozygotes ( p = .001). Reduced synthesis of tryptophan in the central nervous system may contribute to reports of fatigue in women with IBS. Understanding genetic risk factors for fatigue may elucidate preemptive strategies to reduce fatigue in individuals with IBS.

KEYWORDS:
catechol-O-methyltransferase; fatigue; genetic polymorphisms; irritable bowel syndrome; serotonin reuptake transporter; tryptophan hydroxylase

PMID:
30309244
DOI:
10.1177/1099800418806055

 

[Murph]

Thought this one was interesting in the light of the recent theories by Dr Robert Phair on a possible gentic dysfunction leaving ME/CFS patients with high Tryptophan levels.

This enzyme is related to breaking trp down into serotonin though, different to the one Phair has identiifed that breaks trp into kynurenine.

 

[andyguitar]

Thanks for posting that @Murph, I missed it until just now.

 

[bertiedog]

Only one SNP, TPH2 rs4570625, was significantly associated with fatigue

Well I have IBS plus of course fatigue which seems resistant to any permanent change for the better and I am G/T for the quoted SNP.

Pam

 

[andyguitar]

Well then @bertiedog this maybe of considerable significance to your health problems. If i remember correctly you posted something about 2 other genes recently. Was it the SERT transporter and another one that was associated with muscle pain? I first got interested in Tryptophan Hydroxylase when looking into some possible reasons why some medicinal plants seem to work. White Peony came up as something that has a reputation in China/Japan for the successful treatment of CFS. When I read about it, what jumped off the page was the fact that in animal studies it inhibited trp realease and inhibited the 'expression' of Trp Hydroxylase. So if those studies are relevant to humans what we maybe looking for is something that is produced when trp is broken down that is acting as a poision. But as always this will not be the answer for everyone. Could be for @bertiedog though.

 

[bertiedog]

Well then @bertiedog this maybe of considerable significance to your health problems. If i remember correctly you posted something about 2 other genes recently. Was it the SERT transporter and another one that was associated with muscle pain? I first got interested in Tryptophan Hydroxylase when looking into some possible reasons why some medicinal plants seem to work. White Peony came up as something that has a reputation in China/Japan for the successful treatment of CFS. When I read about it, what jumped off the page was the fact that in animal studies it inhibited trp realease and inhibited the 'expression' of Trp Hydroxylase. So if those studies are relevant to humans what we maybe looking for is something that is produced when trp is broken down that is acting as a poision. But as always this will not be the answer for everyone. Could be for @bertiedog though.

Do you remember which thread the discussion would have been in?

Pam

 

[bertiedog]

@andyguitar I just looked up the IDO2 gene which Robert Phair talks about and I am heterozygous for 2 of the 3 SNPs but not sure if that is what you are referring to. Haven't found the SERT info yet.

Pam

 

[bertiedog]

@andyguitar Have just found my info from Livewello on SLC6A4 gene which is the one regarding the transport of serotonin. I have 3 SNPs that are homozygous and 4 that are heterozygous but 21 SNPs are normal.

Pam

 

[andyguitar]

@bertiedog i was thinking about the SLC6A4 gene. In your case MOA A and MOA B are also likley to be relevant. Both are connected to trp and Serotonin. The association bettween TPH 2 IBS AND CFS.raises an interesting question about what is often called the "Gut-brain connection". It's often reported that sufferers have gut problems and one theory is that the gut problems create brain symptoms. Of course some say it is the brain(or mind) effecting the gut. How about a 3rd possibility? Both problems are independant of each other. Its simply a matter of the same metabolic disorder causing symptoms in the brain and small intestine. The metabolic disorder being a defect with TPH 2 and, in the case of cfs, one or two other enzymes.

 

[bertiedog]

Well then @bertiedog this maybe of considerable significance to your health problems. If i remember correctly you posted something about 2 other genes recently. Was it the SERT transporter and another one that was associated with muscle pain? I first got interested in Tryptophan Hydroxylase when looking into some possible reasons why some medicinal plants seem to work. White Peony came up as something that has a reputation in China/Japan for the successful treatment of CFS. When I read about it, what jumped off the page was the fact that in animal studies it inhibited trp realease and inhibited the 'expression' of Trp Hydroxylase. So if those studies are relevant to humans what we maybe looking for is something that is produced when trp is broken down that is acting as a poision. But as always this will not be the answer for everyone. Could be for @bertiedog th

I have had a look at the properties of White Peony and they look interesting as it is also used for migraines and arthritis and I suffer with both of these too so I have ordered it in tea form and will give it a go and let you know if there is any benefit.

At least one of my son has inherited that SNP and he gets bouts of fatigue but nothing like ME. In his case I have always put it down to too much alcohol at times, he works too hard and he has issues with sleep.

He is also heterozygous for COMT whereas as I am homozygous for that one and I don't think its a good combination to have as its very easy to get over enthusiastic about stuff which can make sleep impossible at times and then I have to revert to a very low dose of clonazapan (1/4 of a 0.5 mg tablet) or I would be awake all night.

Pam

 

[bertiedog]

I know this is off topic but I have also found out that I am homozygous for 12 SNPs relating to Hyperadrenergic POTS which I guess if far from helpful when it comes to energy availability and being actually able to use what energy there is in the body!

Pam

 

[andyguitar]

As this tread has revealed there may be a strong link between IBS and CFS/ME. If that link involves a defect with trp metabolism then there may be one simple and cheap way of improving symptoms. Carbohydrate promotes trp release. That is to say releasing the trp already stored in the body into the bloodstream. So trying a diet that is low in carbs might help. And in particular avoid meals which are carb heavy- pasta for instance. Trying to avoid trp in the diet probably would'nt work and restricting intake of it may cause serious heath problems.Avoiding release spikes seems to me to be the only realistic option.