Membrane-Spanning 4 Domains, Subfamily A, Member 2

Alternative Names

  • MS4A2
  • Fc Fragment of IgE, High Affinity I, Receptor for, Beta Subunit
  • FCER1B
  • Immunoglobulin E Receptor, High Affinity, Beta Polypeptide
  • Fc IgE Receptor, Beta Chain
  • Immunoglobulin E Regulator
  • IGHER
  • IGER
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OMIM Number

147138

Gene Map Locus
11q13

Description

The MS4A2 gene encodes the beta subunit of the high affinity IgE receptor, which is a member of the membrane-spanning 4A gene family. The IgE-receptor, a tetramer composed of an alpha, beta, and 2 disulfide-linked gamma chains, is found on the surface of mast cells and basophils. This receptor is responsible for initiating the allergic response. The allergic response involves the binding of allergen to receptor-bound IgE followed by cell activation and the release of mediators (such as histamine) responsible for the manifestations of allergy. It also induces the secretion of important lymphokines.

Molecular Genetics

The MS4A2 gene is located on the long arm of chromosome 11 at 11q13 and spans 10kb of genomic DNA with a coding sequence consisting of 7 exons. The MS4A2 protein comprises 44 amino acids and weighs 26.534kDa.

Studies suggested that the Glu237Gly variant in the MS4A2 gene could be a risk factor for atopic dermatitis and asthma.

Epidemiology in the Arab World

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Other Reports

Kuwait

Hijazi et al. (1998) investigated the presence of IgE receptor FceRIB polymorphism, Leu181/Leu183, LL (wild type being Ile181/Val183, NN), and its association with asthma in Kuwaiti Arabs, using an allele refractory mutation screening (ARMS) test. A total of 52 families each with at least one clinically confirmed child of asthma were included in this study. Blood samples were obtained from 221 subjects (96 asthmatics and 125 non-asthmatics). In the 221 subjects screened for the presence of FceRIB polymorphism (181/183), 48% (107/221) subjects were found to have genotype LL (variant sequence Leu181/Leu183), 49% (109/221) were heterozygous (NL) and 3% (6/221) were homozygous (NN, Ile18l/Val183). Of the 442 chromosomes screened, the L-sequence (Leu181/Leu183) was detected in 72% chromosomes (320/442) while the N-sequence (Ile181/Vall83) was found in 122 chromosomes (28%). Homozygous LL genotype was detected in 48% (46/96) asthmatic subjects compared to 31% (39/125) in non-asthmatics. A total of 52% (50/96) of asthmatics were found to be heterozygous (NL) while 69% (86/125) of non-asthmatics were heterozygous. Only six subjects were found to be a homozygous NN genotype and they were equally divided into the asthmatic and non-asthmatic groups. In 11/52 families mothers of the asthmatic children were themselves asthmatic and 3/11 asthmatic mothers had homozygous LL genotype. On the other side, 80% of the homozygous LL asthmatics showed a positive skin prick test (SPT) compared with 28% of non-asthmatics with the same genotype. In heterozygous NL asthmatics a positive SPT was found in 60% cases compared to 17% in non asthmatics with the same genotype. The incidence of hay fever (HF) and eczema (E) was also found to be higher in homozygous LL asthmatics compared with the non-asthmatics with the same genotype. Hijazi et al. (1998) concluded that this study reports a high prevalence of IgE receptor FceRIB variants in Kuwaiti Arabs compared with British, Australian and Austrian populations studied before, and the association of Leu18I/Leu183 variant with asthma in Kuwaitis underlines its significance as a risk factor in manifesting the clinical phenotype in this population. Later, Haider and Hijazi (1998) determined the prevalence of two polymorphisms of the high affinity IgE receptor FceRIB gene, intron-2 RasI polymorphism (RsaI_int2) and polymorphism in the UTR of exon 7 (RasI_ex7), in Kuwaiti Arabs using PCR-RFLP. A total of 52 families [200 subjects; 78 asthmatics and 122 non-asthmatics] were studied. A complete linkage of int-2 allele A and ex-7 allele 2 was detected in the studied Kuwaiti population, similarly int-2 allele B and ex-7 allele 1 were found to be co-inherited in a given individual unlike Caucasians, Australian and Aboriginal populations. The frequency of int-2 allele A and ex-7 allele 2 was found to be 49% and that of int-2 allele B and ex-7 allele 1 was 51% in the Kuwaiti population. Genotypes BB (1,l) were detected in 23% asthmatic cases and there was no difference between asthmatic and non-asthmatic groups. Genotypes AA (2,2) were detected in 24% asthmatics and in 20% non-asthmatics. Heterozygous AB (1,2) genotypes were detected in 53% of asthmatics and 55% non-asthmatics, respectively. The incidence of hay fever (HF), eczema (E) and a positive skin prick test (SPT) was determined in asthmatic and non-asthmatic subjects with different genotypes. A considerably higher incidence of HF, E and SPT was found in all three genotypes of asthmatic subjects compared with the non-asthmatics. Amongst the asthmatics, individuals with genotypes AA (2,2) were found to have a considerably lower incidence of SPT (42%) compared to 83% in individuals with BB (1,l) genotype while in heterozygous (AB, 1,2) asthmatics the incidence of SPT was detected in 76% of the cases. However, no significant differences in the incidence of HF, E and SPT were found amongst individuals with different genotypes in the non-asthmatic group. In the asthmatic group itself, no significant difference in the incidence of HF and E was found amongst the individuals with different genotypes. Allele frequencies of the two FceRIB gene polymorphisms in Kuwaiti Arab population were found to be markedly different from those reported in the Australian general population and in Aboriginal population. Furthermore, Hijazi and Haider (2001) investigated the association of the beta subunit of the high-affinity IgE receptor (FcepsilonRIbeta) variant (Leu 181/Leu 183) with parental consanguinity, maternal vs paternal inheritance, gender, and severity of asthma in 52 Kuwaiti families in whom at least one person had asthma. Using an allele refractory mutation screening (ARMS) test, blood (from 212 subjects, including asthmatic children, their parents and siblings) was tested for the presence of the normal and variant sequence of the IgE receptor FcepsilonRIbeta [homozygous normal sequence (Ile 181/Val 183, NN), the variant sequence (Leu 181/Leu 183, LL) and the heterozygous state NL]. Of the 212 subjects in the 52 families, 99 subjects (25 parents and 74 offsprings) were found to be asthmatic. Mean age of offsprings was 6.4 years (range: 4-12 years). The consanguinity rate was found to be 42% which is close to the overall 54% reported for the Kuwaiti population. Hijazi and Haider (2001) found slightly more asthmatic fathers (27 per cent) than mothers (21 per cent), but this difference is not significant. The male to female ratio amongst the asthmatics was found to be 1.5:1 and no gender effect on the frequency of the homozygous variant was found. Fifty-eight subjects (59%) were found to have severe and 41 (41%) moderate asthma. Significantly more patients with severe asthma (58%) were found to be homozygous for the variant (Leu 181/Leu 183) than those with moderate disease (33%; p < 0.018), leading Hijazi and Haider (2001) to suggest that the presence of FceRIB polymorphism in the homozygous state may contribute not only to an enhanced risk of developing asthma but also to having a more severe disease. Hijazi and Haider (2001) concluded that the results of this study suggest an equal maternal and paternal contribution to the inheritance of asthma and an association of the homozygous variant (Leu 181/Leu 183) of the IgE receptor FcepsilonRIbeta with disease severity.

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