Filaggrin null mutations are associated with atopic dermatitis and elevated levels of IgE in the Japanese population: a family and case-control study.
Filaggrin (FLG) plays an important role in the barrier function of the skin. Several loss-of-function mutations in the FLG gene have been identified in patients with ichthyosis vulgaris, and these null mutations are associated with atopic dermatitis (AD) development. In this study, we examined tag single nucleotide polymorphisms (tSNPs) and null mutations in FLG for possible associations with AD and atopic phenotypes in a Japanese population. Transmission disequilibrium test of 105 AD families showed that the null allele of the S2554X variant of FLG tended to be overtransmitted to AD-affected offspring; however, the P value did not reach statistical significance. In a case-control comparison of 376 AD cases and 923 nonallergic controls, the null allele of S2554X was significantly associated with AD (P = 0.0012), and the association was strengthened in subjects with AD alone (P = 0.000024). We found that 3321delA and S2554X were also associated with elevated levels of immunoglobulin E (IgE). Combined null mutation carriers were observed more in AD patients and in subjects with high IgE than in control subjects. The combined P value for the family and case-control data was significant for the S2554X and combined null mutations. Our data further support the importance of FLG in AD development.
Enomoto
Hisako
H
Department of Medical Genetics, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, Japan.|Department of Dermatology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.
Hirata
Kenji
K
Department of Medical Genetics, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, Japan.
Otsuka
Kenta
K
Department of Medical Genetics, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, Japan.
Kawai
Toshiharu
T
Department of Medical Genetics, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, Japan.
Takahashi
Takenori
T
Department of Dermatology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.
Hirota
Tomomitsu
T
Laboratory of Genetics of Allergic Disease, RIKEN SNP Research Center, Yokohama, Japan.
Suzuki
Yoichi
Y
Department of Public Health, Chiba University Graduate School of Medicine, Chiba, Japan.
Tamari
Mayumi
M
Laboratory of Genetics of Allergic Disease, RIKEN SNP Research Center, Yokohama, Japan.
Otsuka
Fujio
F
Department of Dermatology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.
Fujieda
Shigeharu
S
Departments of Otorhinolaryngology and Immunology, University of Fukui Faculty of Medical Sciences, Fukui, Japan.
Arinami
Tadao
T
Department of Medical Genetics, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, Japan.
Noguchi
Emiko
E
Department of Medical Genetics, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, Japan. enoguchi@md.tsukuba.ac.jp.
D000293:Adolescent; D000328:Adult; D000483:Alleles; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D018389:Codon, Nonsense; D003876:Dermatitis, Atopic / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D000091344:Filaggrin Proteins; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis* / Q000097:blood; D007223:Infant; D007381:Intermediate Filament Proteins / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*
D018389:Codon, Nonsense; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; D007073:Immunoglobulin E