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Report of the UK and Eire IfHI Members Symposium, 7th April 2006
The first meeting of UK and Eire IfHI members was hosted by Stuart and Elspeth Semple, who offered attendees a warm welcome at their practice in Inveresk, Edinburgh. Most of the attendees were IfHI fellows or masters, and many reunited for the first time since the IfHI conferences in Phoenix.
Nick bowler, FIfHI, former biochemist and CEO of NAP Europe, lead the discussion for the morning, with a presentation based on his research over the last two years. Entitled “Surfing the genome with a blood type microscope,” and giving attendees a taste of what may be to come in future developments, he described the functional genomics of critical illness and injury in relation to blood group. The basis behind many of the studies that have found such a link is the haplotype, a set of single nucleotide polymorphisms (SNPs) found to be statistically associated as a group on a single chromatid (half of a chromosome). In terms of blood group, a haplotype in someone who is blood group O would be OO, the same as their genotype, one O gene inherited from each parent. The haplotype for someone who is AB could be AB or BA, depending on which gene was expressed more strongly. The haplotype for someone who is blood group A would be AA if they are homozygous, but a heterozygous individual with blood group A could have a haplotype of AO or OA. The strength of expression of certain genes may depend on environmental conditions.
This view of genetic expression is now challenging the existing dominant/recessive theory of blood groups (A and B being co-dominant and O being recessive), which was based on agglutination for transfusion purposes: if you have a gene for blood group A, you can’t receive blood from someone with the B antigen as you will certainly have strong IgM antibodies to B (from eating foods containing GalNAc (the A antigen) as a baby, which your immune system does not recognise as ‘self’). Whether you are Ao, AA or A1A2 does not matter in transfusion terms, you can still safely receive blood from a donor with any of those versions of blood group A1. This led to the concept of ‘dominance’ of blood groups A or B over O. Now functional gene expression is considered more important than the dominant and recessive theories, which means having Ao blood may give an individual different characteristics to AA blood. Even those with Ao blood could be different to each other depending on whether they express the A or O gene more strongly, effectively being ‘Ao’ or ‘Oa’, and the characteristics that go with each of those genes that we all relate to individuals with either blood groups O or A.
Nick Bowler then drew a link with Ayurvedic system of dosha categories being a possible ancient haplotyping system, with the 6 different ABO genotypes and the 9 possible haplotypes corresponding with the doshas vata, pitta and kapha, including possible combinations such as vata-pitta and pitta-vata as well as pure vata, for example. He pointed out that there are 82 verified genes at the 9q34 locus, the home of ABO blood group, controlling many characteristics that could give significant differences between individuals depending on blood group expression.
If ABO is interesting in genetic terms, ABH secretor status is even more so. Secretion of ABH antigens is under control of two linked genes on gene locus 19q13, another haplotype: a mutation (SNP variant) in one always goes with a mutation in the other. Presence of the secretor gene adds the H antigen (fucose) to red blood cells and body secretions. If this genetic code for secreting H is absent in the genetic material inherited from both parents, the individual will not secrete their red blood cell antigens into their body tissues, which is what we know as an ABH non-secretor. If they inherit the secretor gene from one parent only, they may still have some of the characteristics of a non-secretor: even though they secrete their ABH antigens, it was postulated that they may have some of the metabolic disease associations connected with being a non-secretor (but not necessarily the cell surface antigen-related ones). 19q13 has 288 verified genes related to this locus, even more than the ABO locus. Chromosome 19 has the highest gene density of all human chromosomes, and many of these relate to how the immune system works, which explains the difference between immune response of secretors and non-secretors: the humoral vs. the cellular response (TH1 and TH2). Other potentially genes on this chromosome relate to insulin-dependent diabetes, familial hypercholesterolaemia, and repair of other genes relating to repairing DNA damage from exposure to radiation and to other environmental pollutants.
The probability of having a particular combination of two specific alleles at a given locus can be calculated using a mathematical formula, which suggests that 2/3 of the general population will be heterozygous for secretor status (i.e. having both secretor and non-secretor genes), which may have a significance in itself when compared with homozygote secretors and non-secretors.
Lewis blood group status becomes significant in terms of the less common Lewis negative individuals (5-15%), those who express neither Lewis a nor Lewis b antigens. This is a separate system from ABH expression, but when combined with ABH haplotype and secretor haplotype, there are 20 possible combinations, including variations of the rare Bombay blood group (those who do not express the H antigen on their red blood cells). Using the probability formula described, nearly half the population having a Lewis positive expression (Lewis a+ b- non-secretors, and Lewis a- b+ secretors) will be heterozygous for the Lewis negative allele. The evolution of the blood group genes was discussed, with the linkages of each gene to the survival needs of different groups of people.
The final part of Nick Bowler’s talk related to cancer, with a review of the unitarian or trophoblastic theory that suggests cancerous cells are similar to trophoblasts, a type of embryonic stem cell that attaches the fertilised ovum to the wall of the uterus. Cancerous cells develop in anaerobic conditions as a result of continuous inflammation and not all tumour cells have the capability of inducing new cancers, only the ones which are similar to embryonic stem cells. The most primitive cells are A-like in structure. Loss of cell surface antigens in cancer leads to exposure of the Thompson Friedenreich (T) antigen, the body’s auto antigen against itself. The connection with the T antigen and blood groups A and M appears to relate to a failure of the immune system in individuals with these blood groups to identify the cancer cells, perhaps due to the similarity between primitive embryonic cells and the A and M antigens. There was a lot more information on this topic, which may be detailed in a later entry.
With the morning presentation completed, the assembled company then proceeded to attend to the most important event of the symposium, the lunch provided by Elspeth Semple. A tasty quinoa and vegetable soup, 100% Demeter rye bread/rice cakes/oatcakes, chicken, a selection of goats’ cheeses and other delicacies catered amply for the individuals of various blood groups and secretor status in attendance.
Part II later...
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