ABSTRACT
MUC7 encodes a small salivary mucin, previously called MG2, a glycoprotein with a putative role in facilitating the clearance of oral bacteria. The central domain of this glycoprotein was previously shown to comprise five or six tandemly repeated units of 23 amino-acids which carry most of the O-linked glycans. The polymorphism of these two allelic forms (MUC7*5 or MUC7*6) has been confirmed in this study in which we have analysed a large cohort of subjects (n = 375) of various ethnic origins. We have also identified a novel rare allele with eight tandem repeats (MUC7*8). MUC7*6 was the most common allele (0.78-0.95) in all the populations tested. The tandem repeat arrays of 22 MUC7*5 alleles and 34 MUC7*6 alleles were sequenced. No sequence differences were detected in any of the MUC7*6 alleles. Twenty-one MUC7*5 alleles sequenced lacked the 4th tandem repeat (structure TR12356), while one showed the structure TR12127. The structure of the MUC7*8 allele was TR12343456. Because of the known role of MUC7 in bacterial binding, and thus its potential involvement in susceptibility to chest disease we also tested MUC7 in our previously described series of Northern European atopic individuals with and without associated asthma. The MUC7*5 allele was rarer in the atopic asthmatics than in the atopic non-asthmatics (P = 0.014, OR for no asthma in atopic individuals 3.13, CI 1.01-6.10), and the difference in frequency between all asthmatics and all non-asthmatics was statistically significant (P = 0.009) while there was no difference between atopy and non-atopy (P = 0.199). In this study we also report the electrophoretic analysis of the MUC7 glycoprotein in saliva from individuals of different MUC7 genotype.
Subject(s)
Asthma/genetics , Mucins/genetics , Polymorphism, Genetic , Salivary Proteins and Peptides/genetics , Adult , Amino Acid Sequence , Base Sequence , DNA/analysis , Electrophoresis, Polyacrylamide Gel , Gene Frequency , Genetic Variation , Genotype , Glycoproteins/genetics , Humans , Intercellular Signaling Peptides and Proteins , Molecular Sequence Data , Organometallic Compounds , Peptides , Saliva/chemistry , Sequence Analysis , Tandem Repeat Sequences/geneticsABSTRACT
Most of the genes that encode epithelial mucins are highly polymorphic due to variations in the length of domains of tandemly repeated (TR) coding sequence, the part of the apomucin that is heavily glycosylated. We report here for the first time a difference in the distribution of MUC TR length alleles in chest disease. We examined the distribution of the length alleles of those MUC genes whose expression we have confirmed in the bronchial tree in an age- and sex-matched series of 50 pairs of atopic patients with and without asthma. There was no significant difference in the distribution of alleles of MUC1, MUC4, MUC5AC, and MUC5B. MUC2, however, showed a highly significant difference in distribution. The atopic, nonasthmatic individuals showed an allele distribution that was very different from all our other patient and control groups, this group showing a longer mean allele length. The observations suggest that longer MUC2 alleles may help protect atopic individuals from developing asthma, though the effect may be due to a linked gene. The biological significance of this variation with respect to susceptibility to asthma will merit further investigation, and it will also be important to substantiate this finding on an independent data set.
