Oh yes Kat, to my understanding, you and Paul both have interpreted his original postings correctly. My understanding is that the abstract does indeed have to do with gene variations between people, in a region of the TNF alpha gene called the promoter. The promoter, usually found upstream of the coding region of a gene, is a "non-coding" region of the gene, but it serves a very important gate-keeper function. The job of a gene's promoter region is to allow certain proteins called "transcription factors" to bind, and these in turn will influence how actively that gene is "transcribed" (that is, copied into "messenger RNA". Messenger RNA in turn is "translated" into the specific protein that the gene encoded). Variations in a promoter will not influence the sequence of the protein ultimately made through transcription/translation, but variations in the promoter COULD conceivably influence how transcription factors bind, and thereby COULD influence how much of that protein (the gene product) ultimately gets made. This is greatly simplified, but it is the gist.
see also:
http://www.ncbi.nlm.nih.gov/entrez/query...t_uids=16446172
Aguillon JC, Cruzat A, Aravena O, Salazar L, Llanos C, Cuchacovich M.
Could single-nucleotide polymorphisms (SNPs) affecting the tumour necrosis
factor promoter be considered as part of rheumatoid arthritis evolution?
Immunobiology. 2006;211(1-2):75-84. Epub 2005 Dec 27.
PMID: 16446172
"..The -308 TNF SNP is a mutation that affects the promoter region of the TNF gene. It defines the TNF1 and TNF2 alleles, determining low and high levels of TNF expression, respectively. The presence of the TNF2 allele has also been linked to increased susceptibility to and severity in a variety of autoimmune and inflammatory disorders, including RA, systemic lupus erythematosus, and ankylosing spondylitis. Studies on the functional significance of -308 SNP have detected higher levels of TNF production by cells from TNF2-carrying individuals than cells from TNF1 individuals. .."
As for its association with AS/SpA's - there is a mixed literature, with some folks reporting association of variations at this gene promoter position with AS/SpA (like the abstract just above suggests), but others do not find any association. No clear picture emerges.
I don't see how this would distinguish primary AS from reactive arthritis though
Link to Kimball's BIology page on promoters:
"Promoter Region of DNA, usually on the 5' side of a gene, that is needed for the initiation of the transcription of that gene. RNA polymerase and other transcription factors bind to the promoter."
http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/P/Promoter.html
Best to enjoy that lovely summer weather!
time to get that sunlight!
