2008 Barcelona - European Society of Human Genetics

Molecular and biochemical basis of disease
P06.104
Association study of candidate genes in the chromosome
5p13.1-q11.2 linkage region for familial primary cutaneous
amyloidosis
M. W. Lin 1,2 , C. T. Hsu 1 , C. C. Huang 3 , Y. F. Liu 4 , D. D. Lee 5 , T. T. Liu 4 , C. K.
Wong 5 , S. F. Tsai 6 ;
1 Institute of Public Health, National Yang-Ming University, Taipei, Taiwan,
2 Department of Medical Research & Education, Taipei Veterans General Hospital,
Taipei, Taiwan, 3 Institute of Biomeical Informatics, National Yang-Ming
University, Taipei, Taiwan, 4 VYM Genome Research Center, National Yang-
Ming University, Taipei, Taiwan, 5 Department of Dermatology, Taipei Veterans
General Hospital, Taipei, Taiwan, 6 Division of Molecular and Genomic Medicine,
National Health Research Institutes, Zhunan Town, Miaoli County, Taiwan.
Primary cutaneous amyloidosis (PCA) is a relatively common skin disorder
in South America and Southeast Asia . The pathogenesis of PCA
remains unclear . Most cases of PCA are sporadic but familial aggregation
has been reported from South America and Taiwan . The different
susceptibility among ethnic groups suggests that genetic factor may
play an important role in its pathogenesis .
In our previous study, we performed genome-wide linkage analysis of
familial primary cutaneous amyloidosis using both microsatellite and
Affymetrix GeneChip ® Human Mapping 10K Array and identified significant
linkage evidence (maximum LOD=4.50) for a portion of FPCA
families on chromosome 5. In the candidate region identified by SNP
linkage mapping, there are 12 known genes .
To characterize the susceptibility genes for FPCA, we applied the Illumina
GoldenGate ® Assay to genotype large amounts of functional
SNPs and tagSNPs selected from the HapMap project within or around
candidate genes of significant linkage region on chromosome 5. A total
number of 23 FPCA families with 75 affected and 72 phenotypically
normal subjects and 94 normal control subjects were genotyped
in the study . Several SNPs on NNT, FGF10, HCN1, ITGA1, ITGA2,
NDUFS4, SNAG1 genes demonstrated statistically significant results
(p-value