Analysis Of Genetic Association Of TGFB1 And SMAD4 Genes With Keloid In Malay Population
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Date
2012-02
Authors
Emami, Azadeh
Journal Title
Journal ISSN
Volume Title
Publisher
Universiti Sains Malaysia
Abstract
Keloid is a complex condition with environmental and genetic risk-contributing
factors. Two candidate genes, TGFβ1 and SMAD4, located in the same signaling
pathway are highly expressed in the keloid fibroblast cells. The present study
investigated the association between variants of TGFβ1 and SMAD4 genes using
PCR-RFLP genotyping method. Allele, genotype and haplotype frequencies of these
variants were compared between 100 keloid cases and 100 normal healthy controls.
No statistical significant difference was found between alleles and genotypes of
TGFβ1 variants in the current case-control study in a Malay population, while TGFβ1
haplotypes in contrast showed a strong association with the risk of keloid. The C-C
haplotype, composed of both c.29C>T and -509 T>C variants was observed more
frequently among cases (Corrected p-value = 0.037, OR = 2.07, 95% CI = 0.87-4.93),
showing a 4.5-fold increased risk for keloid. The AG genotype of the SMAD4
c.5131A>G variant showed a statistically significant trend (P-value = 0.0573, OR =
1.75, 95% CI = 0.99-3.13). The C-C haplotype of TGFβ1 variants showed an
increased risk when combined with both alleles of the SMAD4 c.5131A>G variant,
indicating possible interaction of these genes in keloid development. Either of these
variants is most probably causative at the expression level or is in linkage
disequilibrium with other causative variants in a complex pattern together with the
environmental factors that contribute to the condition. There is only one documented report on a relationship between TGFβ1 and keloid with no association in the
Caucasian population, while there has been no report for SMAD4. Therefore, the
present study is the first of its kind showing a strong positive association between
TGFβ1 and SMAD4 variants and keloids in the Malay population.
Description
Keywords
Environmental and genetic