Dermatitis, Atopic, 6

For a clinical description of atopic dermatitis and an overview of linkage studies, see 603165.

Mapping

Beyer et al. (2000) tested for the association and linkage between atopic dermatitis and 5 chromosomal regions: 5q31-q33, 6p21.3, 12q15-q24.1, 13q12-q31, and 14q11.2/14q32.1-q32.3. Marker analysis was performed in 2 Caucasian populations: (i) 192 unrelated German children with atopic dermatitis and 59 nonatopic children, all from a German birth cohort study; parental DNA was tested in 77 of 192 children with atopic dermatitis; (ii) 40 Swedish families with at least 1 family member with atopic dermatitis selected from the International Study of Asthma and Allergy in Children. Beyer et al. (2000) observed evidence for association with the markers D5S436 and D5S643 (1 cM upstream from D5S436) on chromosome 5q31-q33 in the German population. Beyer et al. (2000) noted that Meyers et al. (1994) and Postma et al. (1995) had found linkage of high total serum IgE and bronchial hyperresponsiveness, respectively, to chromosome 5q31.1-q33.3, with the most significant finding for the marker D5S436, the same marker that Beyer et al. (2000) found to be associated with atopic dermatitis. Beyer et al. (2000) also observed linkage for atopic dermatitis to markers on 13q12-q14 (ATOD5; 605844).

Kawashima et al. (1998) investigated linkage and association between gene markers on 5q31-33 and atopic dermatitis in 88 Japanese atopic dermatitis families. Affected sib pair analysis suggested linkage between the IL4 gene (147780) and atopic dermatitis (lod = 2.28). Transmission disequilibrium testing showed a significantly preferential transmission to atopic dermatitis offspring of the T allele of the -590C/T polymorphism of the IL4 gene (p = 0.001). A case-control comparison suggested a genotypic association of the T/T genotype with atopic dermatitis (odds ratio = 1.88, p = 0.01). Since the T allele may be associated with increased IL4 gene promoter activity compared with the C allele, Kawashima et al. (1998) suggested that genetic differences in transcriptional activity of the IL4 gene may influence atopic dermatitis predisposition.

Walley et al. (2001) identified 6 coding polymorphisms in the SPINK5 gene (605010) and found that a glu420-to-lys (E420K; 605010.0004) variant showed significant association with atopy (see 147050), atopic dermatitis, and asthma (see 600807) in 2 independent panels of families. Kato et al. (2003) characterized 8 polymorphisms in SPINK5 exons 13 and 14 in 124 Japanese patients with atopic dermatitis and 110 healthy controls. They found significant associations (p less than 0.03) between 7 of these polymorphisms and atopic dermatitis in Japanese patients, confirming the previous suggestion of an association between SPINK5 and atopic dermatitis. Kato et al. (2003) observed no significant association between SPINK5, including E420K, and serum IgE levels.