What are the SNPs that I can use in clinical applications to determine the prognosis in many connective tissue diseases? And which of these affect the drug therapy for each disease?
Dear Sajedah Ayesh,
The question itself needs further clarification as in: Which CTD are you interested in? what specific outcome you are looking at.
Having said that there are some basic principles
1. If you are looking at SNPs, it means you already know the candidate genes of interest. This is not always true as even now for most diseases the currently explored SNPs in candidate genes explain < 50% of all effect.
2. With regards to drugs, you can look at Pharmacogenetics. For e.g., we looked at Methotrexate pharmacogenetics in predicting response in rheumatoid. Here we already knew as to which 17 genes of AICAR and folate pathway were of interest. (Pharmacogenetics and Genomics 2008;18:1041-1 and Pharmacogenetics and Genomics 2009;19:823-8)
3. The problem with focussing only on SNPs is that you will miss out on epigenetics completely and miss all genes hitherto not described.
4. For these it might be better to do either Transcriptomics (or gene expression studies) or Genome wide association studies (GWAS). A lot of focus seems to be in looking at epigenetic studies looking at areas of cytosine hypomethylation or histone acetylation (for e.g. in Rheumatoid, almost 60 sites have been identified)
A specific framing of question will make it easier to tell as to which type of study is best suited to your query
Hope this helps
regards
Dear Dr.Shankar Subramanian,
thank you very much for your information
yes, as you said doctor there is many issues :
there is some points that I want to understand, please.
what is the SNPs that I can use to determine the efficacy and response to Methotrexate treatment?
about rheumatoid arthritis, what is the possibility of developing rheumatoid arthritis if one has aunt and grandmother with rheumatoid arthritis, is there any practical method to determine the possibility of having rheumatoid arthritis?
Dear Dr Sajedah Ayesh,
I see 3 aspects of your questions and shall tackle them separately.
1. Genetics in RA and role of SNPs: Though various candidate gene studies and GWAS studies have identified many SNPs across the genome, notably in the class II MHC HLA -DR region, all the SNPs explain less than 15% of genetic susceptibility in RA. Identical twins have
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