Vol.2, No.12, 1345-1348 (2010) Health
doi: 10.4236/health.2010.212200
Copyright © 2010 SciRes. Openly accessible at http://www.scirp.org/journal/HEALTH/
Filaggrin mutations are associated with ichthyosis
vulgaris in the Southern Chinese population*
Chang-Xing Li1, Quan Luo2, Xue-Mei Li2, Xi-Bao Zhang2#, Chun-Lei Han1, Ze-Lin Ma1,
Dong-Zi Lin1
1Department of Dermatology, Dongguan Institute of Dermatology, Dongguan, China;
2Department of Dermatology, Guangzhou Institute of Dermatology, Guangzhou, China;
#Corresponding Author: lilichangxing@163.com;
Authors Chang-Xing Li, and Quan Luo contributed equally to this work.
Received 13 October 2010; revised 1 November 2010; accepted 5 November 2010
Filaggrin (FLG) plays an important role in the
epidermal barrier function, which identified in
patients with ichthyosis vulgaris(IV).To study
the genetics of FLG mutations in Southern
Chinese patients with IV. We evaluated the in-
fluence of five mutations (3321 delA, 441delA,
1249 insG, E1795X and S 3296X) in a c ohort of 65
IV Chinese patients and in 100 control individu-
als using the Sequenom® MassARRAY® sys-
tem. The null allele frequency of 3321delA was
52.31%(34/65). FLG mutation 441delA was only
fo u n d i n o n e I V p a t i e n t s . F L G m u t a t i o n s 1249in sG,
E1795X and S3296X were not found in these
patients. These findings show that the mutation
3321delA represent the most frequent genetic
cause in Southern Chinese IV patients. Our
findings confirm and extend the knowledge of
the influence of FLG mutations in IV.
Keywords: Ichthyosis Vulgaris; Southern Chinese
Population; Filaggrin; Mutation
Ichthyosis vulgaris (OMIM 146700) is the most com-
mon ichthyosis with an estimated prevalence of 1:250-
1000, and inherited in a semidominant pattern [1]. Pa-
tients have light grey scaling, keratosis pilaris, increased
palmoplantar markings and associated atopic manifesta-
tions. Involvement is generally mild and may vary greatly
with climate and humidity. There is reduced or absence
of keratohyalin granules in the epidermis [2]. In addition,
there is a decrease or absence of profilaggrin, a major
component of keratohyalin granules [3,4].
FLG is coding gene located in the epidermal differen-
tiation complex on chromosome 1q21 [5]. Recently, mu-
tations in the FLG have been shown to be a major risk
factor for IV and atopic dermatitis(AD) [5,6]. The asso-
ciation of FLG mutations with IV in Northern European,
Japanese, Bangladeshi, Korean, Taiwanese and Singapo-
rean Chinese populations has been confirmed in subse-
quent studies [7-17]. To date, more than different 20 mu-
tations have been identified in different populations, all
leading to a filaggrin deficiency. FLG mutations
3321delA, 441delA, 1249insG, E1795X and S3296X
have been previously reported, from Asia including China,
Japan, Korea, Taiwan [8]. In this study, we identified five
FLG mutations 3321delA, 441delA, 1249insG, E1795X
and S3296X in Southern Chinese IV patients.
2.1 Cases and Controls
DNA samples from 65 IV were of Southern China ori-
gin and recruited with ethical approval and had given their
informed consent. The study was conducted according to
the principles of the Declaration of Helsinki and all appli-
cable local regulations related to protection of human
subjects. The institutional review boards of the respective
institutions approved the study. DNA samples from 100
healthy volunteers were available to serve as controls.
Controls had never been diagnosed with IV or AD and
information from medical records where available.
2.2 Genotyping
Genomic DNA was extracted from peripheral blood
using standard techniques. All SNPs were genotyped by
MassARRAY™ system (Sequenom, San Diego, CA,
http://www.sequenom.com/ ). The iPLEX™ assay was
followed according to manufacturers instructions (http://
www.sequenom.com/ ) using 10 ng of genomic DNA.
The primer sequences are available upon request (primer
sequences in Table 1).
*Supported by Medical Scientific Research Foundation of Guangdong
Province, China
C.-X. Li et al. / Health 2 (2010) 1345-1348
Copyright © 2010 SciRes. Openly accessible at http://www.scirp.org/journal/HEALTH/
Table 1. Primer sequences for all 5 FLG mutations using iPlex chemistry on a MassARRAY platform.
Mutations Polymerase chain reaction primer 1
sequence Polymerase chain reaction primer 2
sequence Extension primer se-
1249 insG
441 delA
2.3 Statistical Analysis
Genotype frequencies between cases and controls
were using the continuity-adjusted chi-square test. The
reported P-values are the results of two-sided tests.
P-values 0.05 were considered to be statistically sig-
nificant. All computations have been performed using
SAS software version 8.01.
A total of 5 polymorphic SNPs across the FLG gene
locus were analysed (Figures 1,2). The minor allele fre-
quencies of the two functional polymorphisms (7638G/G
and 7717.9A/A) located in the FLG gene were 52.31%
and 1.54% in the IV cases and 5.17% and 0% in controls,
respectively. The assay showed good clusters and mass
spectra (Figures 1,2).The null allele frequency of FLG
mutation 3321delA were 52.31% (34/65) and 4% (4/100)
in cases and controls respectively. FLG mutation
441delA was only found in one IV patients. FLG muta-
tion 441delA was not found in the controls. FLG muta-
tions 1249insG, E1795X and S3296X were not found in
these patients and controls. When comparing IV patients
with controls, only 3321delA mutation showed a statis-
tically significant association with IV (χ2 = 49.1718 P <
IV and AD are relatively common heritable skin dis-
eases. Lack of expression of the protein filaggrin has
been shown to predispose to the development of IV and
atopic eczema or dermatitis [5,16]. The filaggrin gene
resides on human chromosome 1q21 within the epider-
mal differentiation complex, a region that also harbours
genes for several other proteins that are important for the
normal barrier function of the epidermis [5].
Recent studies showed that both diseases are closely
related to loss-of-function mutations in the FLG. The
homozygous or compound heterozygous loss-of-function
mutations p.R501X and c.2282del4 in FLG have been
identified in moderate or severe IV patients from Ireland,
Figure 1. FLG mutation 3321del and 441delA genotyped in 65 IV cases and 100 controls using Sequenom Mas-
sARRAY platform. The assay showed good clusters. No obvious genotyping errors were apparent.
C.-X. Li et al. / Health 2 (2010) 1345-1348
Copyright © 2010 SciRes. Openly accessible at http://www.scirp.org/journal/HEALTH/
Figure 2. FLG mutation 3321del and 441delA genotyped in 65 IV cases and 100 controls us-
ing Sequenom MassARRAY platform. Mass spectra of the two functional polymorphisms
(7638G/G and 7717.9A/A) were loss of the A allele. Pausing and probe peaks are indicated
above the graph.
Scotland and the USA [5]. Meanwhile, c.3321delA mu-
tation in FLG were identified as prevalent in Japanese
and Korean IV and AD patients [7,17]. FLG mutation
E1795X was identified in the Taiwanese population [14].
Nonsense FLG mutations (p.S2889X and p.S3296X)
were found in Japan [18]. Recent reports have suggested
FLG mutations 1249insG, 7945delA, Q2147X E2422X
and 441delA were found in Singaporean Chinese IV
patients [15].
In our case-control study, we investigated 3321delA,
441delA, 1249 insG, E1795X and S3296X mutations
which associated with Asian IV patients. With our re-
sults, we demonstrate here that more than 52.31% of IV
patients in our Southern Chinese case series carry one
FLG mutation 3321delA, whereas 4% of ethnically matched
control individuals carry this mutation. Mutation 3321-
delA was firstly reported in a Japanese population [7],
and was absent in the European population and Singa-
porean Chinese patients [8,15]. One mutation, 441-delA,
was a previously unidentified FLG mutation which
might be Singaporean Chinese specific [15]. FLG muta-
tion 441delA was only found in one IV patients in our
case-control study. This mutation may be less common
in the Asian populations. FLG mutations 1249 insG,
E1795X and S3296X were not identified either in pa-
tients with IV or in healthy controls. With our results, we
could not only confirm the strong influence of the FLG
mutations on the pathogenesis of the disease in this pop-
ulation, but also exemplify differences in prevalent ge-
netics of FLG mutations between Europe and Asia.
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