Human population can be categorized into glands and non-secretors based on A, B and H antigen on footing of presence or absence of these blood group antigens in the organic structure fluids and secernments, such as spit, perspiration, cryings, seeds, serum, mucus present in the digestive piece of land or respiratory pits etc. Glands are persons that secrete blood group antigens in their organic structure fluids while non-secretors are the persons that do non release them in their organic structure fluids and secernments.
It is a known fact that ABO blood type is controlled by blood type coding cistrons nowadays on the chromosome 9q34 but the gland position of an person is decided by interaction of a separate cistron ( called releasing cistron ) with these blood type cistrons. The presence of the releasing cistron in a individual ‘s genome makes him a gland and absence makes him a non gland. The cistron is designated as ( Se ) for Glands and ( Se ) for Non-secretors and it is wholly independent of the blood type A, B, AB or O. The persons releasing antigens in the organic structure fluid are designated as ‘ABH glands ‘ in blood Bankss. Persons holding O blood group secrete antigen H, A blood group secrete A and H antigens, B blood group secrete B and H antigens in the fluids.
A gland cistron helps a individual to derive a grade of protection against different environmental conditions particularly the micro vegetation of a peculiar environment and besides the lectins present in them. It helps them in advancing the growing of friendly, stable blood type enteric bacterial ecosystem which depends on the blood type antigens present in the mucous secretion of an person. Gland position does modify saccharides in the fluids nowadays in the organic structure and their secernments and it besides affects and influences the fond regard and continuity of the micro flora nowadays in the organic structure. Glands are at a higher advantage than non-secretors. Non-secretors have a possible wellness disadvantage. They possess many metabolic traits such as saccharide intolerance, immune susceptiblenesss. Different trials are available for finding an person ‘s gland position. Most common trial uses spit or other organic structure fluids of an person for proving the gland position. These trials are based on the rule of Agglutination Inhibition where the antigens are neutralized by the corresponding antibodies so that these antibodies will non be farther be available to neutralize or agglutinate the same antigens shacking on the ruddy blood cells. ELISA could besides be used for finding the presence of the secreted Lewis antigens in the spit or other organic structure fluids.
The allelomorphs Se and se differ in the frequence and have an anthropological value. They occur in different frequence in different populations. They have a high frequence in the American Indiana and a low frequence in the southern Indians. In US 20 % of the population is glands whereas 80 % of the population consist of non-secretors. The merger allelomorph of the FUT2 ( gland type alpha ( 1,2 ) -fucosyltransferase ) cistron at a high frequence and a new se385 allelomorph in a Korean population
SECRETOR AND NON-SECRETOR
A individual releasing blood group antigens into the organic structure fluids and other secernments like spit, seeds, tear, mucose in the digestive piece of land and respiratory pits are named as glands. In similar footings they put their blood type antigens in the organic structure fluids. They secrete antigens harmonizing to their blood type, A secrete antigen A and H, B secret antigen B and H, O secrete antigen O and AB secrete A, B and H antigen. Glands expresses Lewis B ( Leb ) antigens on the RBC where as non-secretor expresses Lewis a ( Le a ) on their RBC.These antigens in the organic structure fluids give extra protection to the person against the assorted micro-organisms and the lectins present all around us.
15- 20 % of the population consists of non-secretor. These single fail to release the blood group antigens in their organic structure fluids hence they become susceptible to bacterial and superficial barm infections. A big no of them sometimes besides suffer from the autoimmune upset. This could besides be correlated with the gland and non-secretor phenotype. The organic structure secernments of glands and non-secretors differ quantitatively and besides qualitatively. The type and measure of the antigens present in it differ among different persons. In some instances the non-secretors may incorporate the A and B antigens in the spit but the measure is less and even quality is really low hence they have similar functional job.
There are certain belongingss which are specific for glands and differ in non-secretors. Some are listed below:
Intestinal alkalic phosphatase activity
ABH gland correlates the activity of alkalic phosphatase and serum alkaline phosphatase nowadays in the bowel. Non-secretors have low activity of alkalic phosphatase and serum alkaline phosphatase which is responsible for the dislocation of fat and absorb calcium.2-5 Low molecular weight alkaline is present in both glands and non-secretors and high molecular weight alkaline phosphatase is present merely is secretors.6
The ABH blood types influence the population of bacteriums shacking in the local locality of the intestine mucin glycoproteins. Bacteria produce enzymes that have the capableness to degrade the terminal sugar of A, B, and H blood antigens and which are consumed as nutrient by them. The B antigen degrading bacteriums produce enzyme to take the terminal alpha-D-galactose and A antigen degrading bacteriums produce enzyme to detach N-acetylgalactosamine which are used as a beginning of nutrient by them.7,8
The gland and the ABO genetic sciences influence each other and consequence upto 60 % of the vWf concentration fluctuation in plasma. Raised degrees of factor VIII and vWf may do thrombotic and bosom disease in future. Glands have the slowest curdling clip, thinnest blood, least inclination of thrombocyte collection, low sum of factor VIII and von Willebrand factor ( vWf ) .9,10 The non-secretors have highest curdling clip, thick blood, high sum of factor VIII and von Willebrand factor ( vWf ) and low hemorrhage clip. The blood viscousness is besides influenced by the gland position of that person.
Phenotype – Lewis
Features of Cloting
Le ( a- b- ) A A maximal action of factor VIII and vWf
Very Low hemorrhage times ( seen in A, B and AB )
Le ( a+ b- ) intermediary action
Low shed blooding times ( seen in O )
Le ( a- b+ ) minimal action of factor VIII and vWf
Very Long shed blooding times ( seen in O )
Blood Type – Lewis and Factors consequence Blood Clotting
ABH non-secretors express low concentration of IgG immunoglobulin.11,12 The secernment of changing concentration of diverse components of the blood group is controlled by the gland cistron and it besides affects the phagocytic activity of the leukocytes which provides an added advantage to the non-secretors. The leukocytes of the non-secretors possess a greater consumption power when compared to the glands. The O and B blood group non-secretors have the highest phagocytic activity.13
The presence of different concentration of anti-I in the an persons serum is affected by the ABO group, gland position and sex of the person. The glands females have a high degree of anti-I in the serum as compared to the males.14 The non-secretor have low degrees of IgA and IgG antibodies and therefore have frequent jobs with the bosom valve.
Geneticss and Biochemical tracts
The secernment of the blood group antigens in the organic structure fluids and other secernments are genetically influenced by certain allelic cistrons. Secretor cistron contains two allelomorphs ( Se ) and ( Se ) . The dominant cistron ( Se ) is present in the homozygous or heterozygous status in the glands which lead to the secernment of antigens into the organic structure fluids. ( Se ) is recessionary allelomorph and is present in non-secretors in the homozygous status. SeSe and seSe produces a dominant gland phenotype and sese produces a recessionary non-secretor phenotype.
Basically three cistrons are responsible for the formation of the A and B antigens. They are viz. ABO, Hh, and Sese cistrons encoding glycosyltransferases which produces the A and B antigens. H antigen nowadays in the person with O blood group is the precursor for the formation of A and B antigens. H antigen Acts of the Apostless as a anchor for A and B antigens. The O cistron is considered as amorphic. The allele Hh and Sese shack on each venue and are closely linked together. It is besides suggested that one of the allelomorph has arisen by the cistron duplicate of the other. The 2nd allelomorph on the same venue is truly rare. The merchandise related to this allelomorph has n’t been discovered yet and hence it is considered as amorph.
The oligosaccharide responsible for the formation of the A and B antigen can be in a simple additive manner or a complex branched manner. Infants A, B and H antigens contain high sum of additive chained oligosaccharide whereas oligosaccharides present in an grownup contain high sum of branched chained oligosaccharides.15
The A and B antigen is synthesized from a common intermediate known as substance H. The transition is carried out by the add-on of a sugar molecule to the non cut downing terminal of the H oligosaccharide ironss. This add-on affects the responsiveness of H antigen.16,17
The ABH substances are secreted in the Urinary respiratory piece of land, GI piece of land by mucose secretory organs shacking at that place. The gland cistron regulates the synthesis of blood group antigens in the secretory organs of little enteric mucous membrane. The glands and non-secretors produce A and B substances which are fundamentally glycoproteins in pylorus and Brunner ‘s secretory organs and bring forth A and B substances those are soluble in intoxicant and glycosphingolipids in nature.18,19,20
The glands besides produce ABH substances in the prostate and breastfeeding mammary glands.20 The secernment of chest is rich in H substance but hapless in substance A and virtually absent in substance B. The synthesis of these components in the pancreas and secretory cells of perspiration secretory organ is non controlled by the gland gene.21 The blood groups substances were besides found in the calyxes and roll uping tubules of the glands ( Se ) but it could non be concluded that whether they are produced by the kidneys or are by and large excreted. These secernments were noticed in the eight to nine hebdomads old salivary secretory organs and tummy and later it appears throughout the GI tract.19,22
Glycosphingolipids transporting the A or B oligosaccharides are present on the membranes of RBC ‘s, epithelial and endothelial cells and are besides present in the plasma in the soluble signifier. The glycoproteins transporting the similar A and B oligosaccharides are responsible for their activity in the organic structure fluids. In the organic structure fluids they are present in the secreted signifier. The A and B oligosaccharides which do non incorporate the bearer proteins are present in the milk and piss.
The chromosome 19 contains FUT 1 and FUT 2 cistrons which code for fucosyltransferase.23 FUT cistrons numbered from 1-7 and signifier bunchs which are responsible for the production of enzymes called as fucosyltranferases. The bunch is located on chromosome 19q13.3. Fucosyltranferase helps in the formation of fucose mediety which is added to the H antigen and farther gylcosylate the A or/and B antigens.24,25
H antigen is a basic blood group antigen present in each and every human being but the content varies in different persons of the same ABO group. A general form indicates that its strength varies as O & gt ; A2 & gt ; A2B & gt ; B & gt ; A1 & gt ; A1B. Water soluble H antigen has been demonstrated in the spit and the organic structure fluids of the persons. H antigens are fucose incorporating glycan units which are present on the glycolipids or glycoproteins shacking on the red blood cell ‘s membrane or in the secernments. The fucosylatedglycans are the substrate for the enzyme glycosytransferases that are responsible for the formation of the Lewis and A, B blood group antigen antigenic determinants.
Glands contain both the allelomorphs whereas non gland contains the “ void allelomorph ” for FUT2 cistron. The FUT 2 cistron codifications for fucosyltranferaseenzyme in the duct gland tissues which lead to formation of antigens in the organic structure secernments and organic structure fluids.
The A and B cistrons produce glycosyltranferase that add sugar to oligosaccharide ironss that is converted to H antigen. The H antigen are constructed on the oligosaccharide concatenation. The oligosaccharide ironss could be of two type: Type 1 and type 2.15 The glycosphingolipids nowadays in the plasma and on the membranes of glandular and parenchymal cells and glycoproteins present on the cell surfaces or organic structure fluids carry either the type 1 or type 2 ironss. The glycolipids antigens present on the RBC contain type 2 ironss.
A cistron encodes N-acetyl-galactosaminyl-transferase and B gene-encodes galactosaminyl-transferase and addA GalNAcA andA GalA in alpha ( 1-3 ) linkages which is Acts of the Apostless on the H cistron transferase. The H cistron produces fucosyltransferase that add fucose to the terminus Galactose molecule of type 2 concatenation. It forms an alpha ( 1-2 ) linkage. A and B antigens are constructed when the A and B transferases attach several sugars to the type 1 or type 2 concatenation substituted with Fucose.26
The gland cistron FUT2 located at 19q13.3 and codifications for the activity of the glycosyltransferasesin concert with the FUT1 cistron coding for H antigen, needed to piece both the ABO and Lewis blood group and are active in mucose secretory organ and goblet cells which interact with each other and lead to secernments of antigens in the fluids.
The look forms of both the cistrons are different. The FUT1 ( H ) cistron is dominantly expressed in the erythroid tissues which lead to the formation of the H enzyme whereas the FUT2 ( gland ) cistron is expressed in the secretory tissues and lead to the formation of gland enzyme. The merchandise of the H enzyme or H cistron resides on the red blood cells and merchandise of gland cistron resides on mucins in secernments.
If an single deficiency these allelomorphs, he/she will non be able to show the above active enzymes therefore they would be deficient of the substrates which are required by the A or B glycosyltransferases. Therefore they would non show the A and B antigenic determinants.
Correlation between Lewis Phenotype and ABH Secretor position
The Lewis typewriting besides helps in happening the ABH gland position. The production of Lewis antigens is genetically controlled. Persons possessing the Lewis ( Le ) cistron would bring forth the Lewis antigens which are carried in the plasma by different substances and are absorbed onto the Red blood Cells nowadays in one ‘s blood.
The ABO determiners and H/h blood groups factors seem to demo structurally corelation to Lewis blood determiners. FUT1 provide the glycans for glycosyltransferases which convert Lewis antigen to ABH antigens. FUT2 allelomorph is expressed in the gland and is responsible for the look of type1 H determiner.
The glands convert their Lewis a antigen to Lewis B therefore they are ( a-b+ ) and the non-secretor are ( a+b- ) as they lack the FUT2 responsible for glycosyltransferase which could change over Lewis a antigen to Lewis B antigen.
Lewis ( Le ) cistron and Secreting ( Se ) cistron interact with each other. Initially Lewisais formed and if Se cistron is absent in an single the Lewisa substance is absorbed on the RBC and the person is typed as Lewisa but in glands the Se cistron controls the activation of the H cistron which causes add-on of an extra sugar to Lewisa which convert it to Lewisb. Glands contain both Lewisa and Lewisb in their plasma but absorb Lewisb preferentially on the ruddy blood cells and the person is typed as Lewisb.
Hence we could construe that presence of Lewis cistron would type an person as Lewisa positive or Lewisb negative or frailty versa. An person could non be positive for both. A individual incorporating both Lewis cistron and Secreting cistron are typed as Lewisa negative and Lewisb positive whereas a individual holding the Lewis cistron but non the gland cistron is typed as Lewisa positive and Lewisb negative. Individual who does non hold Lewis cistron regardless of gland cistron is typed as Lewisa negative and Lewisb negative.27,28
Note: Lewis Double Negative ( LDN ) is a sub type of non glands but Lewis typing can non be used for them to find the ABH gland position.
The presence and absence of the antigens in the organic structure fluids could be detected by Agglutination Inhibition and Lewis typewriting.
Agglutination Inhibition trial could be divided into two parts: –
Part I – Antibody Neutralization:
To finding one ‘s gland position, the spit of the person is mixed by the antiserum ( Anti-A, Anti-B or Anti-H ) available commercially. In glands the soluble substances i.e. blood group antigens will respond with the antibodies present in the antiserum and will acquire neutralized.
Part II – Agglutination Inhibition:
The bed blood cells obtained commercially are added to the trial mixture. In glands agglutination of the RBC do non take topographic point as no free antibodies are available to agglutinate them. All the antibodies have reacted with the soluble antigens present in the spit whereas in non-secretors agglutination would happen upon add-on of the RBC as no blood group antigens are present in the spit so antibodies nowadays in the antiserum are non neutralized and therefore would be free to respond with the trial RBC cells which are added to the trial mixture. Hence agglutination is a negative trial for gland position and positive trial for the non-secretor position.
Note: Anti-H lectin incorporating phytohaemagglutinin virtually specific for human RBC. Thirteen Cucurbitaceaespecies have been investigated for the anti-H activity nowadays in their seed lectins. Lectins has been extracted and purified from Ulexeuropaeus seeds. It could be used to show the H gland position of blood group O person and besides for subgrouping the blood group A persons.
Persons transporting the Lewis cistron produce Lewis antigens that are carried by the plasma and are besides adsorbed on the ruddy blood cells. Lewis antigens do non shack merely on the ruddy blood cells. Initially the cistron gives rise to Lewisa. If Se cistron is present it activates H cistron which interact with the Lewisa and add a sugar to Lewisa and therefore acquire converted it to Lewisb. Both Lewisa and Lewisb in nowadays in the plasma of the glands. If the Se cistron is non present so the Lewisa substance is adsorbed on the ruddy cells and persons are typed as Lewisa.
The gland position of an person could be determined with aid of Lewisa and Lewisb antibodies mixed with an person ‘s spit and detecting the agglutination macroscopically.
Disease Susceptibility among Secretors and Non-secretors
Non-secretors are more prone to the diseases caused by the unwritten bacteriums in the digestive system of an person. It includes ulcers, celiac diseases stomachic carcinoma baneful anaemia etc. It could take to dysplasia or increase in the figure of pits present in the digestive piece of land. Non-secretors are less immune to the infection caused by Helicobacter pylori which could take to the formation of peptic and duodenal ulcers.32,33 It could easy colonise and do redness in the non-secretors.34 The non-secretors lack the blood group antigens in the mucous secretion secernments hence H.pylori attach to the walls of the digestive piece of land and cause infection. The glands have a inclination to release free ABH antigens in their enteric secernments which consequence the bacterial and lectins attachment to the microvilli nowadays in the intestine. The glands produce these antigens and prevent H.pylori fond regard. These antigens act as a steerer in the glands which prevent them from attaching with the host tissues. The non-secretors besides show a lower IgG immune response to the H.pylori. They have utmost rate of hemorrhage and tummy ulcers but correlativity between these complications and the gland position have non been documented yet. The non-secretors are non able to turn off the digestive enzymes and hence they produce big sum of enzyme pepsin and hence are more prone to duodenal ulcers. 50 % of the duodenal ulcers are present in non-secretors. 30-40 % of group O persons are affected by the duodenal ulcers and 15- 20 % are affected by the stomachic ulcers. They show a high hazard factor along with the cistron coding for hyperpepsinogenemia I which impact in the hazard of duodenal ulcers.35,36 Group A persons have a higher inclination of holding stomachic malignant neoplastic disease and baneful anaemia. Statisticss shows that 20 % of the group A persons are affected by stomachic malignant neoplastic diseases and 25 % are affected by the baneful anaemia.
The non-secretors are more prone to unwritten diseases like oral cavity and esophagus malignant neoplastic disease, epithelial dysplasia etc. They have more pits than secretors.37
The ABH non-secretors and Lewis negative ( Le a-b- ) persons have a high hazard of developing insulin dependant diabetes or complications originating from diabetes.38,39 Glands with juvenile diabetes have a low opportunity of developing retinopathy.40 The ABH non glands which are affected by insulin dependant diabetes mellitus, they show average degrees of C3c and C4 is lower as compared to ABH glands.
Metabolic Syndrome X
The Lewis negative work forces are predisposing to syndrome X and prothrombic metamorphosis. They have high degrees of BMI, SBP, triglycerides and low degrees of insulin in serum and plasma glucose while fasting. This relationship is non true for adult females and is merely applicable for the men.41-43
Glands have an added protection against the harmful environmental assaults directed towards our lungs and as usual non-secretors have a wellness disadvantage. They are over represented among the people enduring from influenza viruses A and B, rhinoviruses, respiratory synsytial virus and echinoviruses.44 Glands who are mineworkers or tobacco users do have a protection against the black effects of the coffin nail smoke. Asthma is really common among the persons working in the coal mines. Upon research it was concluded that asthma among them is besides related to the non-secretor phenotype nowadays in them. The non-secretor has a inclination to saw wood and are more prone to COPD ( Chronic Obstructive Pulmonary Disease ) .45
The ABH non-secretor phenotype have a high hazard of developing myocardial infarction and Lewis negative persons have a high hazard of developing chronic bosom disease ( CHD ) and besides ischaemic bosom disease ( IHD ) .46 They contain high degrees of triglycerides.47 Alcoholism has a positive interaction with the Lewis negative persons. Alcohol ingestion is protective in these individuals.48,49
Autoimmune upsets such as Sjogren ‘s syndrome, spondylitis, induration, arthropathy, arthritis, and Grave ‘s disease are more prone in non-secretors.50-52 The ABH non-secretors affected with grave ‘s disease produces high degrees of antitubulin antibodies as compared to glands and are unable to bring forth the H2O soluble glycoproteins in the saliva.53
Fetal Loss and Infertility
ABO antigens are besides found on the sperm of the secretors.54 These are obtained from the seminal secernments present in them. ABO mutual exclusiveness could be between the married woman and hubby if could impact the birthrate of an individual.55,56 This issue has non been decently studied and is hence under research.
The glands and group O persons are immune to Rheumatic febrility and more figure of instances have been recorded in the non-secretors.57,58 Secretor position could besides find whether the arthritic febrility would be followed by streptococcic sore throat or not.59-61
The non-secretors who do non bring forth H2O soluble antigens in the spit are at the hazard of acquiring infected by Neisseria meningcococcal disease.62 The immune capablenesss of the gland provide a comparative protection in the glands. The ABH non-secretors produce low degree of anti-meningococcal salivary IgM antibodies which provide protection to the glands against the microorganism.63
Non-secretors are barriers of candida species and therefore are often affected by the candida infections. The glycocompounds secreted by glands in the organic structure fluids inhibit adhesins present on the barm which are responsible for their adhesion with the organic structure tissues.64-66 This leads to the development of the chronic hyperplastic Candidiasis. Statisticss shows that 68 % on the non-secretors are affected by chronic hyperplastic candidiasis.67 Non-secretor adult females are affected by perennial idiopathic vulvovaginal Candidiasis. An single with a combination of non-secretors and absence of Lewis cistron are at comparative hazard of developing perennial idiopathic vulvovaginal Candidiasis.68
The persons with homozygous active Le allelomorphs ( Le/Le ) and inactive ( se/se ) alleles shows a highest average value of CA19-9 tumour marker.69 The Lewis negative persons irrespective of Se genotype have negative values for CA19-9. The Lewis negative persons have higher average value for DU PAN-2 as compared to Le-positive individuals.70 We can reason that CA 19-9 marker is non an appropriate tumour marker for Le-negative persons but DU-PAN-9 is an appropriate tumour marker.71
Non-secretors show a higher hazard of acquiring perennial urinary piece of land infection ( UTI ) and nephritic cicatrixs as compared to glands. This susceptibleness is higher among negative Lewis subset. Statisticss of a survey done on adult females affected with perennial urinary piece of land infection stated that 29 % of the non-secretor adult females were affected by UTI and 26 % of Lewis ( a-b- ) adult females were affected by the UTI.72-74 The non-secretor phenotype and blood group B and AB phenotype work together to increase the hazard of UTI among adult females. Womans and kids enduring from nephritic marking with and without the antibiotic intervention for UTI are prone to UTI and pyelonephritis.75-77 55-60 % of non-secretors develop nephritic cicatrixs and 16 % on glands develop nephritic scars.78 C-reactive protein degrees, erythrocyte deposit rate and organic structure temperature are higher in the non-secretors that in glands with recurrent UTI.79
It concludes that there exist a statistical association between the person ‘s blood-group gland phenotype and the diseases they are susceptible to. So cognizing your gland position is advantageous as we can utilize the nutritionary addendums more intelligently and efficaciously. It besides makes us cognizant of the diseases, unwellness and metabolic disfunction we are prone to, difference in the degrees of enteric alkalic phosphatase activity, leanings towards blood curdling, tumour markers and different ingredients of chest milk so that we can pull off them before manus and would be prepared for them in the close hereafter.