Re: Genetic Defect / methylation

[Guest guest]

----Original Message Follows----

From: JOSKAT95@...

*******************************

How is this diagnosed? What tests are done? How is it treated?

Kathy -NNY

***********************************************

The gene variants mentioned are not unique to autism nor are the

abnormalities uncommon in the population as a whole. A recent paper

mentioned three genes.... MTHFR, GSTM1 & GSTT1. The autism findings seem to be

comparable to %'s in other publications.

These same abnormalities are mentioned in research on multiple disorders

including allergies and autoimmunity and reactions that involve many other

exposures.

Results:

> > 1. Methylenetetrahydrofolate Reductase (MTHFR) 677 C?T

polymorphism

> > Frequency in Control individuals: 11%

> > Frequency in Autistic Individuals: 16.6%

> > 2. MTHFR 677 C?T /1298 A?C polymorphism

> > Frequency in Control individuals: 15%

> > Frequency in Autistic Individuals: 25%

> > 3. Glutathione-S-Transferase M1 null

> > Frequency in Control individuals: 53%

> > Frequency in Autistic Individuals: 50%

> > 4. Glutathione-S-Transferase T1 null

> > Frequency in Control individuals: 14%

> > Frequency in Autistic Individuals: 29%

> > 5. GST M1/GST T1 null

> > Frequency in Control individuals: 8%

> > Frequency in Autistic Individuals: 16.6%

The frequency of the GSTM1 null genotype ranges from 23 to 62% in different

populations around the world and is approximately 50% in Caucasians, as

reviewed by Cotton et al. (2000).

From PCR and Southern blot analyses, Pemble et al. (1994) showed that the

GSTT1 gene was absent from 38% of the population.

Chen et al. (1996) described a method for simultaneous characterization of

GSTM1 and GSTT1 and studied the genotypes in whites and blacks. The

frequency of the null genotype for GSTM1

(GSTM1-) was higher in whites and that for GSTT1- was higher in blacks. The

observed frequency of the 'double null' genotype was not significantly

different from that predicted, assuming that the 2

polymorphisms are independent and did not differ by race or sex.

-------------------------------

Deth and colleagues suggest that exposure to thimerosal, even in doses as

low as those contained in one vaccine, has the ability to disrupt

methylation. The theory is that certain children are more at risk than

others because they lack the normal ability to excrete metals like

thimerosal in the urine.

Different Pathology

The researcher says he believes the dramatic rise in autism and ADHD cases

over the last few decades can be blamed on mercury poisoning due to

vaccine-related thimerosal exposure. He adds that the fact that autism rates

have not declined following the banning of thimerosal is not proof of its

safety.

" The epidemiological studies are looking at whole populations, and we are

trying to determine what it is about an individual kid that might make him

more susceptible to this exposure, " he tells WebMD.

But Harvard University neurologist Margaret L. Bauman, MD, says the evidence

just isn't there to show a link between mercury exposure and autism.

Last March, Bauman and colleague Karin , MD, published a review of the

research. They noted that while mercury poisoning and autism both affect the

central nervous system, the specific sites of brain involvement and the

brain cell types affected are different in the two disorders. They further

noted that mercury injures the nerves and other organs that are not affected

in autism.

" The pathology that we see in the brains of people with mercury poisoning

just is not consistent with the pathology we see in the autistic brain, "

Bauman tells WebMD. " It is a total mismatch. "

----------------------------------------------

Clin Chem. 2003 Feb;49(2):295-302.

Comment in:

Clin Chem. 2003 Aug;49(8):1416; author reply 1416-7.

Effect of riboflavin status on the homocysteine-lowering effect of folate in

relation to the MTHFR (C677T) genotype.

Moat SJ, Ashfield-Watt PA, Powers HJ, Newcombe RG, McDowell IF.

Cardiovascular Sciences Research Group, Wales Heart Research Institute,

University of Wales College of Medicine, Cardiff, Wales CF14 4XN, United

Kingdom. moatsj@...

BACKGROUND: Riboflavin (vitamin B(2)) is the precursor for FAD, the cofactor

for methylenetetrahydrofolate reductase (MTHFR). MTHFR catalyzes the

formation of 5-methyltetrahydrofolate, which acts as a methyl donor for

homocysteine remethylation. Individuals with the MTHFR 677C-->T mutation

have increased plasma total homocysteine (tHcy) concentrations, particularly

in association with low folate status. It has been proposed that riboflavin

may act together with folate to lower plasma tHcy, particularly in

individuals with the thermolabile MTHFR T variant.

METHODS: We measured B-vitamin status and plasma tHcy in 126 healthy

individuals 20-63 years of age (42 CC, 42 CT, and 42 TT MTHFR genotypes) at

baseline and after three interventions (4 months): placebo plus natural

diet; daily 400 microg folic acid supplement plus natural diet; and

increased dietary folate to 400 microg/day.

RESULTS: At baseline and after nutritional intervention, lower riboflavin

status was associated with increased plasma tHcy concentrations. Plasma tHcy

was 2.6 micromol/L higher in the lowest plasma riboflavin quartile compared

with the highest (P <0.02) and was 4.2 micromol/L higher in the highest

erythrocyte glutathione reductase activation coefficient (EGRAC) quartile

compared with the lowest (P <0.001). This effect was not restricted to those

with the T allele.

Folic acid given as a 400 microg/day supplement appeared to exacerbate a

tendency toward riboflavin deficiency, as suggested by an increase in the

proportion of individuals with EGRAC > or =1.4 from 52% to 65% after

supplementation (P <0.05).

CONCLUSIONS: Folate and riboflavin interact to lower plasma tHcy, possibly

by maximizing the catalytic activity of MTHFR. The effect may be unrelated

to MTHFR genotype.

PMID: 12560354 [PubMed - indexed for MEDLINE]

---------------------------------------------

Curr Pharm Biotechnol. 2004 Feb;5(1):107-18.

Moderate hyperhomocysteinemia and immune activation.

Schroecksnadel K, Frick B, Wirleitner B, Winkler C, Schennach H, Fuchs D.

Institute of Medical Chemistry and Biochemistry, University of Innsbruck,

Fritz Pregl Strasse 3, A-6020 Innsbruck, Austria. dietmar.fuchs@...

Moderate hyperhomocysteinemia is associated with an increased risk of

atherosclerosis, thrombosis and neurodegenerative diseases. Homocysteine

accumulation in the blood can be due to many underlying causes, which may

interact with each other, e.g. genetic disposition and B-vitamin status.

The role of the sulfur-containing amino acid homocysteine in the

pathogenesis of diseases remains unclear, even if many studies suggest a

causal relationship between homocysteine-mediated processes like oxidative

stress, NO-inactivation and endothelial deficiency and atherogenesis.

Proposed mechanisms of action of homocysteine are discussed, and the

question is addressed, whether effects that are attributed to homocysteine,

are not rather the consequence of folate and vitamin B12-deficiency.

Deficiency of these B-vitamins in parallel with moderate

hyperhomocysteinemia is often found in patients with enhanced activation of

the cellular immune system, like Alzheimer's disease, rheumatoid arthritis

and also vascular diseases.

In patients with these diseases an association between homocysteine

metabolism, oxidative stress and immune activation exists. On the one hand

proliferation of immunocompetent cells having an enhanced demand for

B-vitamins leads to the accumulation of homocysteine. On the other hand

macrophages stimulated by TH1-type cytokine interferon-gamma form reactive

oxygen species (ROS), which oxidize antioxidants, lipoproteins and

oxidation-sensitive B-vitamins. Thereby Th1-type immune response could

contribute importantly to the development of hyperhomocysteinemia, and may

also be a major determinant of disease progression.

PMID: 14965213 [PubMed - in process]

BMC Med. 2004 Feb 12;2(1):3. Related Articles, Links

The methylenetetrahydrofolate reductase gene variant C677T influences

susceptibility to migraine with aura.

Lea RA, Ovcaric M, Sundholm J, MacMillan J, Griffiths LR.

Genomics Research Centre, School of Health Science, Griffith University,

Queensland, Australia. l.griffiths@...

BACKGROUND: The C677T variant in the methylenetetrahydrofolate reductase

(MTHFR) gene is associated with increased levels of circulating homocysteine

and is a mild risk factor for vascular disease. Migraine, with and without

aura (MA and MO), is a prevalent and complex neurovascular disorder that may

also be affected by genetically influenced hyperhomocysteinaemia. To

determine whether the C677T variant in the MTHFR gene is associated with

migraine susceptibility we utilised unrelated and family-based case-control

study designs. METHODS: A total of 652 Caucasian migraine cases were

investigated in this study. The MTHFR C677T variant was genotyped in 270

unrelated migraine cases and 270 controls as well as 382 affected subjects

from 92 multiplex pedigrees. RESULTS: In the unrelated case-control sample

we observed an over-representation of the 677T allele in migraine patients

compared to controls, specifically for the MA subtype (40% vs. 33%) (chi2 =

5.70, P = 0.017). The Armitage test for trend indicated a significant dosage

effect of the risk allele (T) for MA (chi2 = 5.72, P = 0.017). This linear

trend was also present in the independent family-based sample (chi2 = 4.25,

Padjusted = 0.039). Overall, our results indicate that the T/T genotype

confers a modest, yet significant, increase in risk for the MA subtype (odds

ratio: 2.0 - 2.5). No increased risk for the MO subtype was observed (P >

0.05). CONCLUSIONS: In Caucasians, the C677T variant in the MTHFR gene

influences susceptibility to MA, but not MO. Investigation into the enzyme

activity of MTHFR and the role of homocysteine in the pathophysiology of

migraine is warranted.

PMID: 15053827 [PubMed - as supplied by publisher]

Mamm Genome. 2002 Sep;13(9):483-92.

Multiple transcription start sites and alternative splicing in the

methylenetetrahydrofolate reductase gene result in two enzyme isoforms.

Tran P, Leclerc D, Chan M, Pai A, Hiou-Tim F, Wu Q, Goyette P, Artigas C,

Milos R, Rozen R.

Department of Human Genetics, McGill University-Montreal Children's

Hospital, Montreal, Quebec, Canada H3H 1P3.

Methylenetetrahydrofolate reductase (MTHFR) reduces

5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, the major carbon

donor in the remethylation of homocysteine to methionine. Mild MTHFR

deficiency, due to a common variant at nucleotide 677, has been reported to

alter risk for several disorders including cardiovascular disease, neural

tube defects, pregnancy complications, and certain cancers. Little is known

about MTHFR regulation, since the complete cDNA and gene sequences have not

been determined. In earlier work, we isolated and expressed a 2.2-kb human

cDNA comprised of 11 coding exons, and we demonstrated that it encoded an

active 70-kDa isoform. However, transcript sizes of approximately 7.5 kb and

9.5 kb and the presence of a second isoform of 77 kDa on Western blots

suggested that cDNA sequences were incomplete. In this report, we

characterized the complete cDNA and gene structure in human and mouse.

Variable 5? and 3? UTR regions were identified, resulting in transcript

heterogeneity. The 5? and 3? termini of the MTHFR cDNA were found to overlap

with the 5? terminus of a chloride ion channel gene (CLCN-6) and the 3?

terminus of an unidentified gene, respectively; this finding has resulted in

finer mapping of MTHFR on Chromosome (Chr) 1p36.3. Ribonuclease protection

assays identified clusters of transcriptional start sites, suggesting the

existence of multiple promoters. MTHFR has several polyadenylation sites

creating 3?UTR lengths of 0.2 kb-5.0 kb or 0.6 kb-4.0 kb in human and mouse,

respectively. In both species, the previously reported exon 1 was redefined

to approximately 3.0 kb in length and shown to be alternatively spliced. An

important splice variant contains novel coding sequences; this cDNA was

expressed and shown to encode the isozyme of 77 kDa. Our results, which

suggest intricate regulation of MTHFR, will facilitate additional regulatory

and functional studies of the different isoforms.

PMID: 12370778 [PubMed - indexed for MEDLINE]

_________________________________________________________________

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[Guest guest]

The gene variant that my son has (I'm nearly positive that it's MTHFR--

it led his doctor to prescribe the B12/folinic acid/betaine protocol,

and inhibits his DNA methyllation) does not necessarily lead to autism.

He has NLD (nonverbal learning disability) and lymphoid nodular

hyperplasia. We just found out yesterday that his neurotypical sister

has the same mutation. She has allergies and chemical sensitivities.

Some people might feel that my son is on the spectrum, but no one would

argue that about my daughter. Nor does she have learning disabilities.

Jane

On Apr 2, 2004, at 8:56 PM, Cheryl B wrote:

> ----Original Message Follows----

> From: JOSKAT95@...

> *******************************

>

> How is this diagnosed? What tests are done? How is it treated?

>

> Kathy -NNY

>

> ***********************************************

> The gene variants mentioned are not unique to autism nor are the

> abnormalities uncommon in the population as a whole. A recent paper

> mentioned three genes.... MTHFR, GSTM1 & GSTT1. The autism findings

> seem to be comparable to %'s in other publications.

>

> These same abnormalities are mentioned in research on multiple

> disorders

> including allergies and autoimmunity and reactions that involve many

> other

> exposures.

>

>

> Results:

>>> 1. Methylenetetrahydrofolate Reductase (MTHFR) 677 C?T

> polymorphism

>>> Frequency in Control individuals: 11%

>>> Frequency in Autistic Individuals: 16.6%

>>> 2. MTHFR 677 C?T /1298 A?C polymorphism

>>> Frequency in Control individuals: 15%

>>> Frequency in Autistic Individuals: 25%

>>> 3. Glutathione-S-Transferase M1 null

>>> Frequency in Control individuals: 53%

>>> Frequency in Autistic Individuals: 50%

>>> 4. Glutathione-S-Transferase T1 null

>>> Frequency in Control individuals: 14%

>>> Frequency in Autistic Individuals: 29%

>>> 5. GST M1/GST T1 null

>>> Frequency in Control individuals: 8%

>>> Frequency in Autistic Individuals: 16.6%

>

> The frequency of the GSTM1 null genotype ranges from 23 to 62% in

> different

> populations around the world and is approximately 50% in Caucasians, as

> reviewed by Cotton et al. (2000).

>

> From PCR and Southern blot analyses, Pemble et al. (1994) showed that

> the

> GSTT1 gene was absent from 38% of the population.

>

> Chen et al. (1996) described a method for simultaneous

> characterization of

> GSTM1 and GSTT1 and studied the genotypes in whites and blacks. The

> frequency of the null genotype for GSTM1

> (GSTM1-) was higher in whites and that for GSTT1- was higher in

> blacks. The

> observed frequency of the 'double null' genotype was not significantly

> different from that predicted, assuming that the 2

> polymorphisms are independent and did not differ by race or sex.

> -------------------------------

> Deth and colleagues suggest that exposure to thimerosal, even in doses

> as

> low as those contained in one vaccine, has the ability to disrupt

> methylation. The theory is that certain children are more at risk than

> others because they lack the normal ability to excrete metals like

> thimerosal in the urine.

>

>

> Different Pathology

>

>

> The researcher says he believes the dramatic rise in autism and ADHD

> cases

> over the last few decades can be blamed on mercury poisoning due to

> vaccine-related thimerosal exposure. He adds that the fact that autism

> rates

> have not declined following the banning of thimerosal is not proof of

> its

> safety.

>

>

> " The epidemiological studies are looking at whole populations, and we

> are

> trying to determine what it is about an individual kid that might make

> him

> more susceptible to this exposure, " he tells WebMD.

>

>

> But Harvard University neurologist Margaret L. Bauman, MD, says the

> evidence

> just isn't there to show a link between mercury exposure and autism.

>

>

> Last March, Bauman and colleague Karin , MD, published a review

> of the

> research. They noted that while mercury poisoning and autism both

> affect the

> central nervous system, the specific sites of brain involvement and the

> brain cell types affected are different in the two disorders. They

> further

> noted that mercury injures the nerves and other organs that are not

> affected

> in autism.

>

>

> " The pathology that we see in the brains of people with mercury

> poisoning

> just is not consistent with the pathology we see in the autistic

> brain, "

> Bauman tells WebMD. " It is a total mismatch. "

>

>

> ----------------------------------------------

> Clin Chem. 2003 Feb;49(2):295-302.

>

>

> Comment in:

> Clin Chem. 2003 Aug;49(8):1416; author reply 1416-7.

>

> Effect of riboflavin status on the homocysteine-lowering effect of

> folate in

> relation to the MTHFR (C677T) genotype.

>

> Moat SJ, Ashfield-Watt PA, Powers HJ, Newcombe RG, McDowell IF.

>

> Cardiovascular Sciences Research Group, Wales Heart Research Institute,

> University of Wales College of Medicine, Cardiff, Wales CF14 4XN,

> United

> Kingdom. moatsj@...

>

> BACKGROUND: Riboflavin (vitamin B(2)) is the precursor for FAD, the

> cofactor

> for methylenetetrahydrofolate reductase (MTHFR). MTHFR catalyzes the

> formation of 5-methyltetrahydrofolate, which acts as a methyl donor for

> homocysteine remethylation. Individuals with the MTHFR 677C-->T

> mutation

> have increased plasma total homocysteine (tHcy) concentrations,

> particularly

> in association with low folate status. It has been proposed that

> riboflavin

> may act together with folate to lower plasma tHcy, particularly in

> individuals with the thermolabile MTHFR T variant.

>

> METHODS: We measured B-vitamin status and plasma tHcy in 126 healthy

> individuals 20-63 years of age (42 CC, 42 CT, and 42 TT MTHFR

> genotypes) at

> baseline and after three interventions (4 months): placebo plus natural

> diet; daily 400 microg folic acid supplement plus natural diet; and

> increased dietary folate to 400 microg/day.

>

> RESULTS: At baseline and after nutritional intervention, lower

> riboflavin

> status was associated with increased plasma tHcy concentrations.

> Plasma tHcy

> was 2.6 micromol/L higher in the lowest plasma riboflavin quartile

> compared

> with the highest (P <0.02) and was 4.2 micromol/L higher in the highest

> erythrocyte glutathione reductase activation coefficient (EGRAC)

> quartile

> compared with the lowest (P <0.001). This effect was not restricted to

> those

> with the T allele.

>

> Folic acid given as a 400 microg/day supplement appeared to exacerbate

> a

> tendency toward riboflavin deficiency, as suggested by an increase in

> the

> proportion of individuals with EGRAC > or =1.4 from 52% to 65% after

> supplementation (P <0.05).

>

> CONCLUSIONS: Folate and riboflavin interact to lower plasma tHcy,

> possibly

> by maximizing the catalytic activity of MTHFR. The effect may be

> unrelated

> to MTHFR genotype.

>

> PMID: 12560354 [PubMed - indexed for MEDLINE]

> ---------------------------------------------

>

> Curr Pharm Biotechnol. 2004 Feb;5(1):107-18.

>

>

> Moderate hyperhomocysteinemia and immune activation.

>

> Schroecksnadel K, Frick B, Wirleitner B, Winkler C, Schennach H, Fuchs

> D.

>

> Institute of Medical Chemistry and Biochemistry, University of

> Innsbruck,

> Fritz Pregl Strasse 3, A-6020 Innsbruck, Austria.

> dietmar.fuchs@...

>

> Moderate hyperhomocysteinemia is associated with an increased risk of

> atherosclerosis, thrombosis and neurodegenerative diseases.

> Homocysteine

> accumulation in the blood can be due to many underlying causes, which

> may

> interact with each other, e.g. genetic disposition and B-vitamin

> status.

>

> The role of the sulfur-containing amino acid homocysteine in the

> pathogenesis of diseases remains unclear, even if many studies suggest

> a

> causal relationship between homocysteine-mediated processes like

> oxidative

> stress, NO-inactivation and endothelial deficiency and atherogenesis.

> Proposed mechanisms of action of homocysteine are discussed, and the

> question is addressed, whether effects that are attributed to

> homocysteine,

> are not rather the consequence of folate and vitamin B12-deficiency.

> Deficiency of these B-vitamins in parallel with moderate

> hyperhomocysteinemia is often found in patients with enhanced

> activation of

> the cellular immune system, like Alzheimer's disease, rheumatoid

> arthritis

> and also vascular diseases.

>

> In patients with these diseases an association between homocysteine

> metabolism, oxidative stress and immune activation exists. On the one

> hand

> proliferation of immunocompetent cells having an enhanced demand for

> B-vitamins leads to the accumulation of homocysteine. On the other hand

> macrophages stimulated by TH1-type cytokine interferon-gamma form

> reactive

> oxygen species (ROS), which oxidize antioxidants, lipoproteins and

> oxidation-sensitive B-vitamins. Thereby Th1-type immune response could

> contribute importantly to the development of hyperhomocysteinemia, and

> may

> also be a major determinant of disease progression.

>

> PMID: 14965213 [PubMed - in process]

>

> BMC Med. 2004 Feb 12;2(1):3. Related Articles, Links

>

>

> The methylenetetrahydrofolate reductase gene variant C677T influences

> susceptibility to migraine with aura.

>

> Lea RA, Ovcaric M, Sundholm J, MacMillan J, Griffiths LR.

>

> Genomics Research Centre, School of Health Science, Griffith

> University,

> Queensland, Australia. l.griffiths@...

>

> BACKGROUND: The C677T variant in the methylenetetrahydrofolate

> reductase

> (MTHFR) gene is associated with increased levels of circulating

> homocysteine

> and is a mild risk factor for vascular disease. Migraine, with and

> without

> aura (MA and MO), is a prevalent and complex neurovascular disorder

> that may

> also be affected by genetically influenced hyperhomocysteinaemia. To

> determine whether the C677T variant in the MTHFR gene is associated

> with

> migraine susceptibility we utilised unrelated and family-based

> case-control

> study designs. METHODS: A total of 652 Caucasian migraine cases were

> investigated in this study. The MTHFR C677T variant was genotyped in

> 270

> unrelated migraine cases and 270 controls as well as 382 affected

> subjects

> from 92 multiplex pedigrees. RESULTS: In the unrelated case-control

> sample

> we observed an over-representation of the 677T allele in migraine

> patients

> compared to controls, specifically for the MA subtype (40% vs. 33%)

> (chi2 =

> 5.70, P = 0.017). The Armitage test for trend indicated a significant

> dosage

> effect of the risk allele (T) for MA (chi2 = 5.72, P = 0.017). This

> linear

> trend was also present in the independent family-based sample (chi2 =

> 4.25,

> Padjusted = 0.039). Overall, our results indicate that the T/T genotype

> confers a modest, yet significant, increase in risk for the MA subtype

> (odds

> ratio: 2.0 - 2.5). No increased risk for the MO subtype was observed

> (P >

> 0.05). CONCLUSIONS: In Caucasians, the C677T variant in the MTHFR gene

> influences susceptibility to MA, but not MO. Investigation into the

> enzyme

> activity of MTHFR and the role of homocysteine in the pathophysiology

> of

> migraine is warranted.

>

> PMID: 15053827 [PubMed - as supplied by publisher]

>

> Mamm Genome. 2002 Sep;13(9):483-92.

>

>

> Multiple transcription start sites and alternative splicing in the

> methylenetetrahydrofolate reductase gene result in two enzyme isoforms.

>

> Tran P, Leclerc D, Chan M, Pai A, Hiou-Tim F, Wu Q, Goyette P, Artigas

> C,

> Milos R, Rozen R.

>

> Department of Human Genetics, McGill University-Montreal Children's

> Hospital, Montreal, Quebec, Canada H3H 1P3.

>

> Methylenetetrahydrofolate reductase (MTHFR) reduces

> 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, the major

> carbon

> donor in the remethylation of homocysteine to methionine. Mild MTHFR

> deficiency, due to a common variant at nucleotide 677, has been

> reported to

> alter risk for several disorders including cardiovascular disease,

> neural

> tube defects, pregnancy complications, and certain cancers. Little is

> known

> about MTHFR regulation, since the complete cDNA and gene sequences

> have not

> been determined. In earlier work, we isolated and expressed a 2.2-kb

> human

> cDNA comprised of 11 coding exons, and we demonstrated that it encoded

> an

> active 70-kDa isoform. However, transcript sizes of approximately 7.5

> kb and

> 9.5 kb and the presence of a second isoform of 77 kDa on Western blots

> suggested that cDNA sequences were incomplete. In this report, we

> characterized the complete cDNA and gene structure in human and mouse.

> Variable 5? and 3? UTR regions were identified, resulting in transcript

> heterogeneity. The 5? and 3? termini of the MTHFR cDNA were found to

> overlap

> with the 5? terminus of a chloride ion channel gene (CLCN-6) and the 3?

> terminus of an unidentified gene, respectively; this finding has

> resulted in

> finer mapping of MTHFR on Chromosome (Chr) 1p36.3. Ribonuclease

> protection

> assays identified clusters of transcriptional start sites, suggesting

> the

> existence of multiple promoters. MTHFR has several polyadenylation

> sites

> creating 3?UTR lengths of 0.2 kb-5.0 kb or 0.6 kb-4.0 kb in human and

> mouse,

> respectively. In both species, the previously reported exon 1 was

> redefined

> to approximately 3.0 kb in length and shown to be alternatively

> spliced. An

> important splice variant contains novel coding sequences; this cDNA was

> expressed and shown to encode the isozyme of 77 kDa. Our results, which

> suggest intricate regulation of MTHFR, will facilitate additional

> regulatory

> and functional studies of the different isoforms.

>

> PMID: 12370778 [PubMed - indexed for MEDLINE]

_________________________________________________________________

Responsibility for the content of this message lies strictly with

the original author(s), and is not necessarily endorsed by or the

opinion of the Research Institute.

[Guest guest]

In a message dated 4/3/04 3:57:03 AM Eastern Daylight Time,

clbro66@... writes:

> ***********************************************

> The gene variants mentioned are not unique to autism nor are the

> abnormalities uncommon in the population as a whole. A recent paper

> mentioned three genes.... MTHFR, GSTM1 & GSTT1. The autism findings seem to

> be comparable to %'s in other publications.

>

> These same abnormalities are mentioned in research on multiple disorders

> including allergies and autoimmunity and reactions that involve many other

> exposures.

>

>

>

So they reflect immune dysfunction? Kathy -NNY

[Guest guest]

> In a message dated 4/3/04 3:57:03 AM Eastern Daylight Time,

> clbro66@h... writes:

>

>

> > ***********************************************

> > The gene variants mentioned are not unique to autism nor are the

> > abnormalities uncommon in the population as a whole. A recent

paper

> > mentioned three genes.... MTHFR, GSTM1 & GSTT1. The autism

findings seem to

> > be comparable to %'s in other publications.

> >

> > These same abnormalities are mentioned in research on multiple

disorders

> > including allergies and autoimmunity and reactions that involve

many other

> > exposures.

> >

> >

> >

>

> So they reflect immune dysfunction? Kathy -NNY

Not directly. They can be a part of what makes a person more

susceptable. The MTHFR gene becomes a problem when combined with a

deficient diet because homocysteine becomes elevated and is

considered a marker of inflammation/folic deficiency.