Saturday, March 30, 2019
Secretors And Non Secretors In Human Population Biology Essay
glands And Non Secretors In Human Population Biology EssayHuman universe fecal matter be categorized into glandy organs and non-secretors. They be categorized on the stem of mien or absence of the declivity crowd antigens (A, B and H) in the remains fluids and secernments, such as tongue, sweat, tears, semen, broth serum, mucus be in the digestive tract or respiratory cavities etcetera Secretors argon psyches that publish prodigal theme antigens in their dust fluids while non-secretors be the respective(prenominal)s that do non secrete them in their body fluids and discriminations.It is a known fact that aboriginal bank line compositors case is controlled by assembly line caseful coding ing ablaze(p)ients grant on the chromo to a greater extent or less 9q34 further the secretor side of an individual is decided by action of a separate ingredient (called secreting agent) with these line of business sign genes. The strawman of the secreting gene in a persons genome makes him a secretor and absence makes him a non secretor. The gene is designated as (Se) for Secretors and (se) for Non-secretors and it is entirely in interdependent of the blood casing A, B, AB or O. The individuals secreting antigens in the body fluid argon designated as ABH secretors in blood banks. Individuals having O blood host secrete antigen H, A blood group secrete A and H antigens, B blood group secrete B and H antigens in the fluids.A secretor gene helps a person to gain a degree of protection against diverse environsal conditions especially the micro plant of a particular environment and likewise the lectins interpret in them. It helps them in promoting the growth of friendly, stable blood example enteric bacterial eco governing body which depends on the blood type antigens present in the mucus of an individual. Secretor status does alter the carbohydrates present in the body fluids and their secretions and consequently it also strickles a nd influences the attachment and persistence of the micro flora present in the body. Secretors atomic number 18 at a exalteder good than non-secretors. Non-secretors pass a potential health disadvantage. They possess many metabolous traits such as carbohydrate intolerance, tolerant susceptibilities. Different demonstrates atomic number 18 accessible for determining an individuals secretor status. Most super C turn up utilises saliva or otherwise body fluids of an individual for testing the secretor status. These tests be establish on the principle of agglutination Inhibition where the antigens atomic number 18 neutralized by the corresponding antibodies so that these antibodies will not be further be available to neutralize or agglutinate the same antigens residing on the red blood prison cells. ELISA could also be utilize for determining the presence of the secreted Lewis antigens in the saliva or other body fluids.StatisticsSeries, Place annexeNumber Tested% Sec retor% Non-secretorFrequencyFrequencyNegroes, parvenue York(5)178126.96.36.1990.62Danes,Copenhagen(6)26374.026.00.490.51Japanese,Japan.42475.724.30.510.49Germans,Berlin(7)36378.022.00.530.47Poles,Poland(8)8879.421.60.540.46Whites, New York(9)7482.417.60.580.42Finns, Helsinki(10)19686.313.70.630.37American, Indians,New Mexico(11)69188.8.131.520.12American, Indians, Utah(12)79100.001.000The alleles Se and se differ in the frequency and ready an anthropological value. They sink in variant frequency in different populations. They imbibe a high frequency in the American Indiana and a petty(a) frequency in the southern Indians. In US 20% of the population is secretors whereas 80% of the population consist of non-secretors. The fusion allele of the FUT2 (secretor type alpha(1,2)-fucosyltransferase) gene at a high frequency and a immature se385 allele in a Korean populationSECRETOR AND NON-SECRETORA person secreting blood group antigens into the body fluids and other secretions c atomi c number 18 saliva, semen, tear, mucous in the digestive tract and respiratory cavities are named as secretors. In quasi(prenominal) terms they put their blood type antigens in the body fluids. They secrete antigens according 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. Secretors expresses Lewis b (Leb) antigens on the RBC where as non-secretor expresses Lewis a (Le a) on their RBC.These antigens in the body fluids give additional protection to the individual against the various microorganisms and the lectins present all around us.15- 20% of the population consists of non-secretor. These individual fail to secrete the blood group antigens in their body fluids therefrom they become susceptible to bacterial and superficial yeast infections. A oversized no of them sometimes also suffer from the autoimmune disorder. This could also be correlated with the secretor and non-secretor phenotype. The body s ecretions of secretors and non-secretors differ quantitatively and also qualitatively. The type and quantity of the antigens present in it differ among different individuals. In some cases the non-secretors may contain the A and B antigens in the saliva however the quantity is less and even quality is very low t hence they have similar functional problem.There are certain properties which are specific for secretors and differ in non-secretors. Some are listed below intestinal base-forming phosphatase useABH secretor correlates the activity of alkaline phosphatase and serum alkaline phosphatase present in the intestine. Non-secretors have low activity of alkaline phosphatase and serum alkaline phosphatase which is prudent for the breakdown of fat and assimilate calcium. Low molecular(a) weight alkaline is present in twain secretors and non-secretors and high molecular weight alkaline phosphatase is present only is secretors.Bacterial floraThe ABH blood types influence the pop ulation of bacteria residing in the local vicinity of the catgut mucin glycoproteins. Bacteria turn enzymes that have the capability to degrade the terminal clams of ABH blood type antigens and which are consumed as food by them. The B antigen contaminating bacteria elevate enzyme to detach the terminal alpha-D-galactose and A antigen degrading bacteria produce enzyme to detach N-acetylgalactosamine which are used as a source of food by them.Blood clottingThe secretor and the indigene genetics influence each other and influence the variance of the germ plasm concentration of vWf upto 60%. Raised levels of instrument VIII and vWf may vitrine thrombotic and means ailment in future. Secretors have the slowest clotting time, thinnest blood, least(prenominal) endeavor of platelet aggregation, low kernel of name out VIII and von von Willebrand factor (vWf). The non-secretors have highest clotting time, thick blood, high amount of factor VIII and von Willebrand factor (vWf) and low bleeding time. The blood viscosity is also influenced by the secretor phenotype.Lewis PhenotypeClotting CharacteristicsLe (a- b-)highest activity of factor VIII and vWfShortest bleeding times (especially in A, B and AB)Le (a+ b-) intercede activityShorter bleeding times (especially for O)Le (a- b+) lowest activity of factor VIII and vWfLongest bleeding times (especially for O)Lewis Blood image and Clotting FactorsImmunoglobulin levelsABH non-secretors have low levels of IgG immunoglobulin. The secretion of different concentration of different components of the blood group fondnesss is controlled by the secretor gene and it also affects the phagocytic activity of the leucocytes which provides an added advantage to the non-secretors. The leucocytes of the non-secretors possess a great ingestion power when compared to the secretors. The O and B blood group non-secretors have the highest phagocytic activity.The presence of level of anti-I in the serum of an individual is a lter by the ABO group, secretor status and sex of the individual. The secretors females have a high level of anti-I in the serum as compared to the males. The non-secretor have low levels of IgA and IgG antibodies and hence have frequent problems with the heart valve. genetics and Biochemical pathwaysThe secretion of the blood group antigens in the body fluids and other secretions are genetically influenced by certain allelomorphic genes. Secretor gene contains two alleles Se and se. Se is dominant and hence is present in the homozygous or heterozygous condition in the secretors which booster cable to the secretion of antigens into the body fluids. se is recessive allele and is present in non-secretors in the homozygous condition. SeSe and seSe produces a dominant secretor phenotype and sese produces a recessive non-secretor phenotype. basically three genes are responsible for the formation of the A and B antigens. They are namely ABO, Hh, and Sese genes encoding glycosyltransferas es which produces the A and B antigens. H antigen present in the individual with O blood group is the precursor for the formation of A and B antigens. H antigen act as a backbone on which the A and B antigens are built up. The O gene is considered as amorphic. The allele Hh and Sese reside on each locale and are fast linked together. It is also suggested that one of the allele has arisen by the gene duplicate of the other. The H allele is responsible for the production of H antigen on which antigen A and B are built. The second allele on the same locus is really rare. The product related to this allele hasnt been discovered yet and hence it is considered as amorph.The oligosaccharide responsible for the formation of the A and B antigen can embody in a simple linear fashion or a complex branched fashion. Infants A, B and H antigens contain high amount of linear chained oligosaccharide whereas oligosaccharides present in an adult contain high amount of branched chained oligosacchar idesThe A and B antigen is synthesized from a common intermediate known as substance H. The conversion is carried out by the addition of a sugar molecule to the non reducing end of the H oligosaccharide arrange. This addition affects the matchivity of H antigen.The ABH substances are secreted in the Urinary respiratory tract, gastrointestinal tract by mucous glands residing there. The secretor gene regulates the deduction of blood group antigens in the superficial glands of gastric and small intestinal mucosa. The secretors and non-secretors produce A and B substances which are basically glycoproteins in pylorus and Brunners glands and produce A and B substances those are meltable in alcohol and glycosphingolipids in nature.The secretors also produce ABH substances in the prostate and lactating mammary glands. The secretion of breast is rich in H substance but scant(p) in substance A and about absent in substance B. The synthesis of these substances in the exocrine acini of pa ncreas and secretory cells of sweat gland is not controlled by the secretor gene. The blood groups substances were also detected in the pile up tubules and calyxes of the secretors but it could not be concluded that whether they are produced by the kidneys or are generally excreted. These secretions were noticed in the eight to nine weeks anile salivary glands and stomach and later it appears throughout the gastrointestinal tract.Glycosphingolipids carrying the A or B oligosaccharides are present on the membranes of RBCs, epithelial and endothelial cells and are also present in the blood blood plasma in the soluble form. The glycoproteins carrying the similar A and B oligosaccharides are responsible for their activity in the body fluids. In the body fluids they are present in the secreted form. The A and B oligosaccharides which do not contain the carrier proteins are present in the milk and urine.The chromosome 19 containsFUT 1 and FUT 2 genes which code for fucosyltransferase. FUT genes figed from 1-7 and form clusters which are responsible for the production of enzymes called as fucosyltranferases. The cluster is located on chromosome 19q13.3. Fucosyltranferase helps in the formation of fucose moiety which is added to the H antigen and further gylcosylate the A or/and B antigens.H antigen is a basic blood group antigen present in each and every human being but the content varies in different individuals of the same ABO group. A general pattern indicates that its potential varies as OA2A2BBA1A1B. Water soluble H antigen has been demonstrated in the saliva and the body fluids of the individuals.H antigens are fucose containing glycan units which are present on the glycolipids or glycoproteins residing on the erythrocytes membrane or in the secretions. The fucosylatedglycans are the substrate for the enzyme glycosytransferases that are responsible for the formation of the epitopes for A, B and Lewis blood group antigens.Secretors contain both the alleles whereas non secretor contains the null allele for FUT2 gene. The FUT 2 gene codes for fucosyltranferaseenzyme in the exocrine tissues which baksheesh to formation of antigens in the body secretions and body fluids.The A and B genes produce glycosyltranferase that add sugar to oligosaccharide chains that is shifted to H antigen. The H antigen are constructed on the oligosaccharide chain. The oligosaccharide chains could be of two type Type 1 and type 2. 1 carbon of the terminal 6-carbon sugar b-D-galactose (Gal) is linked to the number 3 carbon of subterminalN-acetyl-glucosamine(GlcNAc) in Type 1 chains and to the number 4 carbon of GlcNAc in Type 2 chains. The glycosphingolipids present in the plasma and on the membranes of glandular and parenchymal cells and glycoproteins present on the cell surfaces or body fluids carry either the type 1 or type 2 chains. The glycolipids antigens present on the RBC contain type 2 chains.A gene-specifies N-acetyl-galactosaminyl-transferase and the B gene-specifies galactosaminyl-transferase and add GalNAc andGal respectively in alpha (1-3) linkages to the same Gal which is acted on by the H gene transferase. The H gene produces fucosyltransferase that add fucose to the terminal Galactose molecule of type 2 chain. It forms an alpha (1-2) linkage. A and B antigens are constructed when the A and B transferases attach respective sugars to the type 1 or type 2 chain substituted with Fucose.The A alleles encode UDP-GalNAc Fuc alpha1-2 Gal alpha1-3 N-acetyl-D-galactosaminyltransferase (alpha 1-3 GalNActransferase or histo-blood group A transferase). The B alleles encode UDP-Gal Fuc alpha1-2 Gal alpha 1-3 galactosyltransferase (alpha 1-3 galactosyltransferase or histo-blood group B transferase). O alleles encode proteins without glycosyltransferase functionThe secretor gene FUT2 located at 19q13.3 and codes for the activity of the glycosyltransferasesin concert with the FUT1 gene coding for H antigen, needed to take on both the ABO and Lewis blood groups.They are restless in places like goblet and mucous gland cells which move with each other and go bad to secretions of antigens in the fluids.The expression patterns of both the genes are different. The FUT1 (H) gene is dominantly expressed in the erythroid tissues which lead to the formation of the H enzyme whereas the FUT2 (secretor) gene is expressed in the secretory tissues and lead to the formation of secretor enzyme. The product of the H enzyme or H gene resides on the erythrocytes and product of secretor gene resides on mucins in secretions.If an individual deficiency these alleles, he/she will not be able express the above active enzymes thence they would lack the substrates for the A or B glycosyltransferases and hence they would not express the A and B epitopes.Relationship of ABH Secretor status and Lewis systemLewis typing is sometimes used for the de facto determination of the ABH secretor status. The production of Lewis antigens is geneti cally controlled. Individuals possessing the Lewis (Le) gene would produce the Lewis antigens which are carried in the plasma by different substances and are absorbed onto the inflamed blood Cells present in ones blood.The ABO determinants and H/h blood groups determinants are structurally related to Lewis blood determinants. FUT1 provide the glycans for glycosyltransferases which convert Lewis antigen to ABH antigens. FUT2 allele is expressed in the secretor and is responsible for the expression of type1 H determinant.The secretors 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 convert Lewis a antigen to Lewis b antigen.Lewis (Le) gene and Secreting (Se) gene interact with each other. Initially Lewisais formed and if Se gene is absent in an individual the Lewisa substance is absorbed on the RBC and the individual is typed as Lewisa but in secretors the Se gene controls the activation of the H gene which causes addition of an additional sugar to Lewisa which convert it to Lewisb. Secretors contain both Lewisa and Lewisb in their plasma but absorb Lewisb preferentially on the red blood cells and the individual is typed as Lewisb.Hence we could interpret that presence of Lewis gene would type an individual as Lewisa positive or Lewisb proscribe or iniquity versa. An individual could not be positive for both. A person containing both Lewis gene and Secreting gene are typed as Lewisa prohibit and Lewisb positive whereas a person having the Lewis gene but not the secretor gene is typed as Lewisa positive and Lewisb negative. Individual who does not have Lewis gene regardless of secretor gene is typed as Lewisa negative and Lewisb negative.Note Lewis Double Negative (LDN) is a sub type of non secretors but Lewis typing cannot be used for them to contain the ABH secretor status.Detection methodsThe presence and absence of the antigens in the body fluids could be detected by Agglutination Inhibition and Lewis typing.Agglutination Inhibition test could be divided into two parts-Part I Antibody neutralisation reactionTo determining ones secretor status, the saliva of the individual is sundry(a) by the antiserum (Anti-A, Anti-B or Anti-H) available commercially. In secretors the soluble substances i.e. blood group antigens will react with the antibodies present in the antiserum and will get neutralized.Part II Agglutination InhibitionThe bed blood cells obtained commercially are added to the test mixture. In secretors agglutination of the RBC do not take place as no free antibodies are available to agglutinate them. All the antibodies have reacted with the soluble antigens present in the saliva whereas in non-secretors agglutination would occur upon addition of the RBC as no blood group antigens are present in the saliva so antibodies present in the antiserum are not neutralized and hence would be free to react with the test RBC cells which are added to the test mixture. Hence agglutination is a negative test for secretor status and positive test for the non-secretor status.Note Anti-H lectin containing phytohaemagglutinin virtually specific for human RBC. Thirteen Cucurbitaceaespecies have been investigated for the anti-H activity present in their seed lectins. Lectins has been extracted and purified from Ulexeuropaeus seeds. It could be used to demonstrate the H secretor status of blood group O individual and also for subgrouping the blood group A individuals.Lewis typingIndividuals carrying the Lewis gene produce Lewis antigens that are carried by the plasma and are also adsorbed on the red blood cells. Lewis antigens do not reside only on the red blood cells. Initially the gene gives rise to Lewisa. If Se gene is present it activates H gene which interact with the Lewisa and add a sugar to Lewisa and hence get converted it to Lewisb. two Lewisa and Lewisb in present in the plasma of the secre tors. If the Se gene is not present then the Lewisa substance is adsorbed on the red cells and individuals are typed as Lewisa.The secretor status of an individual could be determined with help of Lewisa and Lewisb antibodies mixed with an individuals saliva and observing the agglutination macroscopically. complaint Susceptibility among Secretors and Non-secretorsDigestive systemNon-secretors are more disposed to the complaints caused by the spoken bacteria in the digestive system of an individual. It includes ulcers, celiac diseases gastric carcinoma pernicious anemia etc. It could lead to dysplasia or increase in the number of cavities present in the digestive tract. Non-secretors are less resistant to the infection caused by Helicobacter pylori which could lead to the formation of peptic and duodenal ulcers. It could easily colonize and cause inflaming in the non-secretors. The non-secretors lack the blood group antigens in the mucus secretions therefore H.pylori attach to th e walls of the digestive tract and cause infection. The secretors have a tendency to secrete free ABH antigens in their intestinal secretions which effect the bacterial and lectins bail bond to the microvilli present in the gut. The secretors produce these antigens and act as a hawkish disadvantage from encumbering H.pylori attachment. These antigens act as a decoy in the secretors which prevent them from attaching with the host tissues. The non-secretors also show a start IgG immune response to the H.pylori. They have excessive rate of bleeding, perforation and larnment of stomach ulcers but correlation between these complications and the secretor status have not been record yet. The non-secretors are not able to turn off the digestive enzymes and hence they produce large amount 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 individuals are modify by the duodenal ulcers and 15- 20 % are affected by the gastric ulcers. They act as a multiplicative assay factor with the gene coding for hyperpepsinogenemia I which impact in the risk of duodenal ulcers. Group A individuals have a higher(prenominal)(prenominal) tendency of having gastric cancer and pernicious anemia. Statistics shows that 20% of the group A individuals are affected by gastric cancers and 25% are affected by the pernicious anemia.Oral pathologyThe non-secretors are more prone to oral diseases like mouth and esophagus cancer, epithelial dysplasia etc. They have more cavities than secretors.DiabetesThe ABH non-secretors and Lewis negative (Le a-b-) individuals have a high risk of growing insulin dependent diabetes or complications arising from diabetes. Secretors with juvenile diabetes have a low chance of growth retinopathy. The ABH non secretors which are affected by insulin dependent diabetes mellitus the mean level of C3c and C4 is lower as compared to ABH secretors.Metabolic Syndrome XThe Lewis ne gative men are predisposing to syndrome X and prothrombic metabolism. They have high levels of BMI, SBP, triglycerides and low rather fasting levels of serum insulin and plasma glucose. This relationship is not true for women and is only applicable for the men.Respiratory trunkSecretors have an added protection against the harmful environmental assaults directed towards our lungs and as ordinary non-secretors have a health disadvantage. They are over represented among the state suffering from influenza viruses A and B, rhinoviruses, respiratory synsytial virus and echinoviruses. The secretors who are miners or smokers do receive a protection against the disastrous effects of the derriere smoking. Asthma is very common among the individuals working in the coal mines. Upon question it was concluded that asthma among them is also related to the non-secretor phenotype present in them. The non-secretor has a tendency to snore and are more prone to COPD (Chronic Obstructive pneumoni c Disease).Heart diseaseThe ABH non-secretor phenotype have a high risk of growing myocardial infarction and Lewis negative individuals have a high risk of developing degenerative heart disease (CHD) and also ischemic heart disease (IHD). They contain high levels of triglycerides. Alcoholism has a positive fundamental interaction with the Lewis negative individuals. Alcohol consumption is protective in these individuals.Autoimmune DiseaseAutoimmune disorders such as ankylosing spondylitis, reactive arthritis, psoriatic arthropathy, Sjogrens syndrome, multiple sclerosis, and Graves disease are more prone in non-secretors. The ABH non-secretors affected with graves disease produces high levels of antitubulin antibodies as compared to secretors and are unable to produce the body of water soluble glycoproteins in the saliva.Fetal Loss and InfertilityABO antigens are also found on the sperm of the secretors. These are obtained from the seminal secretions present in them. ABO incompati bility could exist between the wife and husband if could affect the fertility of an individual. This issue has not been properly studied and is therefore under(a) research. rheumatoid FeverThe secretors and group O individuals are resistant to Rheumatic fever and more number of cases have been recorded in the non-secretors. Secretor status could also determine whether the rheumatic fever would be followed by streptococcal pharyngitis or not.Neisseria speciesThe non-secretors who do not produce water soluble antigens in the saliva are at the risk of acquiring infected by Neisseria meningcococcal disease. The immune capabilities of the secretor provide a congeneric protection in the secretors. The ABH non-secretors produce low level of anti-meningococcal salivary immunoglobulin M antibodies which provide protection to the secretors against the microorganism.Candida speciesNon-secretors are barriers of candida species and therefore are frequently affected by the candida infections. T he glycocompounds secreted by secretors in the body fluids inhibit adhesins present on the yeast which are responsible for their adhesion with the body tissues. This leads to the development of the chronic hyperplastic Candidiasis. Statistics shows that 68% on the non-secretors are affected by chronic hyperplastic candidiasis. Non-secretor women are affected by recurrent idiopathic vulvovaginal Candidiasis. An individual with a junto of non-secretors and absence of Lewis gene are at relative risk of developing recurrent idiopathic vulvovaginal Candidiasis.Tumor MarkersThe individuals with inactive Se (se/se) alleles and homozygous active Le alleles (Le/Le) allele have a highest mean value of CA19-9 tumour home run. The Lewis negative individuals irrespective of Se genotype have negative set for CA19-9. The Lewis negative individuals have higher mean value for DU PAN-2 as compared to Le-positive individuals. We can conclude that CA 19-9 marker is not an appropriate tumor marker f or Le-negative individuals but DU-PAN-9 is an appropriate tumor marker.Bacteria Urinary Tract InfectionsNon-secretors are at a higher risk of getting recurrent urinary tract infection (UTI) and renal scars as compared to secretors. This susceptibility is higher among negative Lewis subset. Statistics of a study done on women affected with recurrent urinary tract infection stated that 29% of the non-secretor women were affected by UTI and 26% of Lewis (a-b-) women were affected by the UTI. The non-secretor phenotype and blood group B and AB phenotype work together to increase the risk of UTI among women. Women and children suffering from renal scarring with and without the antibiotic treatment for UTI are prone to UTI and pyelonephritis. 55-60% of non-secretors develop renal scars and 16% on secretors develop renal scars. C-reactive protein levels, erythrocyte sedimentation rate and body temperature are higher in the non-secretors that in secretors with recurrent UTI.ConclusionIt co ncludes that there exist a statistical association between the individuals blood-group secretor phenotype and the diseases they are susceptible to. So knowing your secretor status is advantageous as we can use the nutritional supplements more intelligently and effectively. It also makes us aware of the diseases, nausea and metabolic dysfunction we are prone to, difference in the levels of intestinal alkaline phosphatase activity, propensities towards blood clotting, tumor markers and different ingredients of breast milk so that we can manage them before hand and would be prepared for them in the near future.