Can you be a combo of CC, CT, TT

[jules2551]

I was wondering with the IL28B test can you be a combination of one or more of these polymorphisms or phenotypes?  I was just doing some research on it.  Not finding an answer to my question.  Any input would be greatly appreciated!

Thanks Jules

[candyce1953]

Thanks Will you always lift my spirits!
Hoping I am in that percentage

[eureka254]

IL28B polymorphisms are expressed in twos (ie. CC/CT/TT) because human DNA is diploid; in other words, the IL28B gene normally exists in pairs, one on each chromosome.  Human DNA is comprised of 4 neucleotide variations, AGC&T, but the genotypes on the human gene do not necessarily correlate directly in any way to hcv RNA (viral RNA actually has a different variation or neuclotides that includes uracil, which human DNA does not).

The theory is that the interleukin gene variations within human DNA triggers unique individual amino-acid responses depending on the polymorphism within the IL28B gene... whether or not they will make similar discoveries about IL28A SNPs is unknown.  

Thus far, most treatment meds being developed are centered on interrupting the RNA sequencing in hcv replication; as host-gene polymorphisms and their subsequent pathologies get worked out, it's conceivable that future treatments will be exploring modifying host responses to the virus rather than modifying the virus itself.

I haven't come across any research directly correlating IL28B genotype to viral load, but there is evidence that CC genotype for SNP rs12979860 is associated with higher incidence of spontaneous clearance in vertical transmission, so not out of the realm of possibility that genotype may also impact host viral load.  As desrt says, though, 4 week tx response still trumps all this IL28B genotype stuff.

[somuchmore2]

VL 800,000

Which surprised me because back in 2002 it was >4million.

Liver is stage 3 or 4 as I did suffer a major varices bleed back in 2007.

[willbb]

jules &candyce:
There was an ad-hoc analysis done in the telaprivir(Incivek trial) as it pertains to the IL28B gene .

What gene you have has less significance when adding the  P. I. however interesting enough ,,the CT and TT  faired quite well with the addition of the third drug.
Will


http://hepatitiscnewdrugs.blogspot.com/2011/05/hepatitis-ctelaprevir-ups-response.html


The allele distribution was consistent with previous reports about treatment-naive patients, with 49% of patients having the CT allele, 33% the CC allele, and 18% the TT allele, said Dr. Jacobson, chief of the division of gastroenterology and hepatology at New York-Presbyterian Hospital/Weill Cornell Medical Center in New York.
SVR rates among patients with the CC allele were 90% with 12-week telaprevir plus PR, 84% with 8-week telaprevir plus PR, and 64% with PR alone.
The largest improvements in response, however, were observed in patients with the CT and TT alleles – the addition of telaprevir doubled and even tripled SVR rates, Dr. Jacobson said. SVR rates in the CT group reached 71% with 12-week telaprevir plus PR, 57% with 8-week telaprevir plus PR, and 25% with PR alone. SVR rates in the TT group were 73%, 59% and 23%, respectively.
"The impact of 12- and 8-week telaprevir appear to be greater in patients with a T allele than with a CC allele," he said.


Rapid virologic response (RVR) rate, defined as undetectable HCV RNA at week 4, and eRVR, defined as undetectable HCV RNA at weeks 4 and 12, were improved with the telaprevir-based regimens across all IL-28B genotypes, compared to PR alone.


The RVR rates in patients with the CC allele were 84% with the 12-week telaprevir regimen plus PR vs. 71% with 8-week telaprevir plus PR and 16% for PR alone. Corresponding data for the CT allele were 60%, 62%, and 2%, and for the TT allele were 59%, 50%, and 0%.
Most eRVR patients achieved SVR to telaprevir with PR in all allele groups: CC at 95%, CT at 92%, and TT at 80%, Dr. Jacobson said. Patients with the CT and TT alleles who did not achieve eRVR had lower SVR rates than CC patients.


Further research, including studies on nonwhites, is needed to confirm these findings, Dr. Jacobson said.
Dr. Jacobson disclosed numerous financial relationships with industry including grant support and other financial benefits from Tibotec and Vertex Pharmaceuticals, which are developing telaprevir together. Several coauthors also disclosed financial relationships including employment with Vertex.

[candyce1953]

Wow I am a bit confused
I am 1b, TT
865 VL
Grade 2/ stage 2
Infected hep C for 41 years
Hi Desrt
Currently 58
Naive
Starting 3xTX January 31

I know TT isn't so good to have for SOC
But am hoping the 3x Vic will help

What is the name of the other blood test for the other DNA markers
And is that for interfereon or ribivarin ?
Thank you

[jules2551]

I know that pre-tx viral load is probably one of the weakest predictors.....but there does seem to be a correlation between VL and polymorphisms.  Just my opinion in looking at journals

jules

[desrt]

Should have said, "Pre-tx viral load is probably one of the weakest predictors..."

[desrt]

No, it would be epressd something like CC/TT/AA for the three SNPS that I mentioned. You can take a look at the graph about half way down the page of this study to see this notation.

http://www.natap.org/2011/HCV/021611_02.htm

It gets confusing because at some sites on this gene CC is the best result and at others TT is th best result. It's good to brush up on your RNA building blocks so you know what  AGC&T stand for. Once you've brushed up on your viral RNA you can restudy ribavirin  -  specifically this part:

http://en.wikipedia.org/wiki/Ribavirin

"For this reason, when ribavirin is incorporated into RNA, as a base analog of either adenine or guanine, it pairs equally well with either uracil or cytosine, inducing mutations in RNA-dependent replication in RNA viruses. Such hypermutation can be lethal to RNA viruses."

Viral load is probably one of the weakest predictors of SVR. Viral genotype and host genotype remain the strongest pre-tx predictors and 4 week viral load the strongest predictor once you've started tx.

[jules2551]

What was your VL before starting tx?  Just curious

[somuchmore2]

My experience with Il28B has been interesting but not precise. My test came up as TT so hardest case to cure.  However, it is week 24 and I have been UND wk-4, 8, 12, 20, etc.....

Also, I am Geno1A who failed treatment twice (1997 & 2002). The Invicek did the job well this time.

[jules2551]

It seems that IL28A gene is closely related to the 28B gene.  These two genes combines listed a whole slew (?) of polymorphisms with about 10 letters...Ex: CCTTGGCCCCTGGGAA.  it's honestly mind-boggling.  I am just curious the reason why they put so much weight on the IL28B test vs. the IL28A test.  

And Desrt...if you had both CC and TT results...where does that put you?  Like NY said...CT?  And also for GT lB patients, it seems that viral load plays a part in chances of SVR.  The "higher" the baseline VL the better chance, say CC, for SVR.  The "lower" the baseline VL the worst chance, say TT for SVR.

Just reading medical journals and was overwhelmed with all of the in depth information.  Tricky stuff here

Jules

[desrt]

If you're talking about the test currently available from LabCorp  -  no. This test only takes the results for one SNP (rs12979860) on the interleukin 28B gene. On this test you either have to be CC, CT, or TT.
There are, however, two other sites on this gene (rs8099917 and rs12980275) that seem to have significance. If you were able to take this type of test  -  yes, you could have both CC and TT results.

[eureka254]

IL28B has become synonymous with the blood test, but in actuality IL28B is a gene (interleukin-28b) on the human chromosome.  In years past, as I understand it, the IL28B test when it was first developed looked at one single nucleotide polymorphism (SNP) in that part of the gene, but as research and testing has continued to develop, they have found other SNPs in and around the IL28B gene that correlate to hcv treatment response and clearance.

So, as more and more SNPs are found and research can correlate the data to treatment response, it won't be just whether or not you are CC on that first SNP, but testing is now becoming available to look at other polymorphisms to further fine tune predicting response -- in other words, different parts of the gene with different variations (some SNPs are C/T, some are C/G, etc.).  Additional IL28B SNP results will most likely become more and more part of an equation.  Hope that makes sense. ~eureka

[EyesofBlue55]

Merrybe is the other member that talked about this at one time-I will try to find the post about the two tests

[jules2551]

Yes NYgirl...that would make sense!  But I could of sworn I saw somewhere who was CC and TT on their IL28B test.  I just wonder how that could have happened.  I've googled this all day and can't find anything about multiple phenotypes.

[EyesofBlue55]

According to Vertex, the response-guided therapy will allow many patients to take a shortened course of therapy (24 weeks rather than the standard 48 weeks for just peginterferon alfa plus ribavirin), due to undetectable HCV levels at 4 and 12 weeks. Vertex stated in its press release that it estimated more than 60 percent of new or relapsed patients will be able to take the shortened treatment course.

Vertex is also currently investigating a possible 12-week total treatment course for patients with a certain genetic mutation. Previous studies have shown that these patients, who have a so-called “CC genotype,” tend to respond very well to hepatitis C treatment. Vertex estimates that this could include around a third of previously untreated patients.

Taken from the FDA  website

[nygirl7]

IDK I think there are three types with TT being the worst, I always assumed CT was in the middle or closer to the CC.  

Now with Tele it's not as important as it once was with just interferon/riba.  They did not have these tests when we treated years ago. I dont think they matter that much if you are on triple.

[EyesofBlue55]

There are actually 2 genetic tests that are being used now .The IL28B polymorphism test is one of them.It can predict your response to treatment.In this test it is better to have the CC alleye.With TT being the not -so-good to have.The other test it is better to have the TT alleye.I dont know what this test is called-maybe some of the more experienced members can answer for you.Maybe thats why your Dr said 'CC and TT"Your dr should give you more info as to why he said this.

[stormy456]

Husband's test says he's a CC and TT

[nygirl7]

Jules wouldn't a CC and a TT = a CT?