23&me people - do you have this particular TNF gene?

Post by **tex** » Fri Apr 03, 2015 9:28 am

You're most welcome. Another identical match. It's beginning to appear that the authors of that first article have a vivid imagination.

We investigated the C4 gene CNV in 1,241 European Americans, including patients with systemic lupus erythematosus (SLE), their first-degree relatives, and unrelated healthy subjects, by definitive genotyping and phenotyping techniques. The gene copy number (GCN) varied from 2 to 6 for total C4, from 0 to 5 for C4A, and from 0 to 4 for C4B. Four copies of total C4, two copies of C4A, and two copies of C4B were the most common GCN counts, but each constituted only between one-half and three-quarters of the study populations. Long C4 genes were strongly correlated with C4A (R=0.695; P<.0001). Short C4 genes were correlated with C4B (R=0.437; P<.0001). In comparison with healthy subjects, patients with SLE clearly had the GCN of total C4 and C4A shifting to the lower side. The risk of SLE disease susceptibility significantly increased among subjects with only two copies of total C4

So according to their claims, everyone who was reported so far is living with a relatively high risk of developing SLE. Really? Call me a skeptic, but I kinda doubt that.

And if the gene copy number of 2 is so uncommon, why is it so common here?

The problem with the current state of understanding of these data (in general) and what they represent is that science's understanding is far too shallow and too limited to be of much practical use for helping to guide decision-making processes regarding important lifestyle changes.

Maybe it's just me but it seems that there are so many aspects of medical science where information is virtually exploding these days. But the analysis of these data is where the rubber meets the road, and that segment of the industry seems to be having a mighty tough time unsuccessfully trying to keep up. Many (actually most) of the conclusions that are published won't stand up to careful scrutiny in the light of day.

But it's all interesting, and playing with this stuff is how we learn.

Tex

Zizzle · Post by **Zizzle** » Fri Apr 03, 2015 10:15 am

Hmmm, Kathy is identical to me and Deb is identical to Tex. Donna appears to have 2 C4A genes and no C4B genes.

I was expecting others to have more copies of these genes than me. Then again, perhaps having fewer is a risk factor for MC?

At least Donna's result suggests you can have more than one of each.

The description of these genes is most interesting, and makes me think it plays a role in the pathophysiology of MC.

C4a anaphylatoxin is a mediator of local inflammatory process. It induces the contraction of smooth muscle, increases vascular permeability and causes histamine release from mast cells and basophilic leukocytes.

http://ghr.nlm.nih.gov/gene/C4A

http://ghr.nlm.nih.gov/gene/C4B

I'm trying to find the SNP for the Lupus mutation...

Zizzle · Post by **Zizzle** » Fri Apr 03, 2015 10:24 am

For those who believe mycoplasma infections may be behind MC -- this newer study showed greater susceptibility among those with C4 deficiency, at least in elderly people.

http://www.ncbi.nlm.nih.gov/pubmed/24638111

Complement C4 deficiency--a plausible risk factor for non-tuberculous mycobacteria (NTM) infection in apparently immunocompetent patients.

This is getting interesting...

And much of this knowledge dates back to 1988:
http://www.ncbi.nlm.nih.gov/pubmed/3078708

Here's more detail on the SLE susceptibility: http://www.ncbi.nlm.nih.gov/pubmed/14719377

I'm still trying to figure out the null allele.

Zizzle · Post by **Zizzle** » Fri Apr 03, 2015 11:27 am

Well, you all may be safe from Lupus after all. A follow-up study in 2012 suggested that low C4 gene counts were not an independent risk factor for Lupus. They have to be in combination with either the HLA-DRB1 or TNF-308A genes (which I have both of).

If you want to check your results for them, they are:

rs2187668(A;G) -- HLA-DRB1*0301 allele of the HLA-DQA1 gene

rs1800629(A;G) -- TNF gene known as TNF308a

Boteva et al. (2012) genotyped 1,028 SLE cases, including 501 patients from the UK and 537 from Spain, and 1,179 controls for gene copy number of total C4, C4A, C4B, and the 2-bp insertion SNP (C4AQ0; 120810.0001) resulting in a null allele. The loss-of-function SNP in C4A was not associated with SLE in either population. Boteva et al. (2012) used multiple logistic regression to determine the independence of C4 CNV from known SNP and HLA-DRB1 associations. Overall, the findings indicated that partial C4 deficiency states are not independent risk factors for SLE in UK and Spanish populations. Although complete homozygous deficiency of complement C4 is one of the strongest genetic risk factors for SLE, partial C4 deficiency states do not independently predispose to the disease.

Full research manuscript: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3309188/

And here's the full history of the C4a gene: http://www.omim.org/entry/120810?search ... hlight=c4a

Post by **tex** » Fri Apr 03, 2015 3:27 pm

When it comes to genetic research, you can probably safely consider a lot of the work published during the last century to be obsolete by now, maybe all of it.

Tex

Zizzle · Post by **Zizzle** » Wed Apr 08, 2015 12:40 pm

Good news! Went for a repeat CBC and my white blood cell counts are back to low-normal ranges . Phew! No hematologist needed!

My integrative medicine doc also prescribed a small 5 mcg dose of generic Cytomel for my borderline low reverse T3. After only 4 days, my body temp rose from 97.4 to 98.4, and my resting heart rate went from 60 BPM or lower to 70 BPM. I imagine my uncomfortably low BP is improving too, because I feel GREAT!! I'm hoping this thyroid boost will also help me taper off my last 1mg of prednisone. The rash on my outer thighs is nearly gone, my skin is less dry, and I'm down to 100 mg Plaquenil/day.

I can't believe I felt like a half-corpse all this time, and all I needed was a slight thyroid boost!