Psoriasis is a chronic, immune-mediated inflammatory skin disease which is cause by a combination of genetic and environmental factors
Prevalence worldwide affects:
-between 0.1 to 5% of the world population
-1-2 % in North America and Europe.
–In China it affects prevalence of 0.123% of individuals. Although the prevalence is lower, it amounts to around 15million people !
Out of 1043 cases in China a family history has been shown to be present in 30% of cases and that it is inherited in 67% of cases.
Even though in identical twins, only 70% of the other twin will be affected if the sibling is affected, a study of genetics is useful in the understanding of the condition.
PREVIOUS GENOMIC STUDIES
1. In 2008, 12 psoriasis susceptibility locations in genes were identified. They are labeled PSORS 1-12 (they were revealed with a technique called genome-wide linkage analysis (GWAS) – since then more than 40 loci have been identified.
PSORS 1 and PSORS 9 associated with Chinese population
2. in 2009 in a study of 1139 cases and 1132 controls:
–LCE (Late Cornified Enveloppe) was identified as a susceptibility gene .
LCE gene codes for a protein of the cornified enveloppe (Stratum Corneum) that have a important role in epidermal terminal differentiation (2009)
in cooperation with Europe in 254 families, 10466 cases and 15880 controls and multiethnichs. 2 genes identified confirmed in European population.
3. Also coding variants called MGST2 (microsomal glutathione S-transferase 2) and LNPEP (leucyl/cystinyl aminopeptidase ) have been identified – however GWAS and linkage analysis were not sensitive enough in revealing the coding variants playing important roles in the pathogenesis of psoriasis.
4. More recently, Prof Zhang XJ and his colleagues (Anhui Medical University, China) did a genomic analysis in the following study.
Study design – Results
1. exome and targeted sequencing study in Han chinese – 7 psoriasis associated common or low frequency missense SNV (Single Nucleotide variant)).
2. genome wide exome array analysis was done on 42760 individuals – revelation of 16 SNP (Single Nucleotide Polymorphism) located in 15 new genes/loci, located in coding regions (exons*)
WHY STUDY GENES INVOLVED IN PSORIASIS ?
Coding genes and (their variants) are related to proteins which contribute to the structure of the psoriasis lesion.
Understanding of genes is therefore important scientifically because it can help to:
-study the pathogenesis
-develop new therapies
-give a prognosis of the disease
-choose a treatment
-manage the condition according to the patient’s individual needs
Pathway from DNA to Protein to Phenotype:
-Intranuclear Genes are coded into Deoxyribonucleic acid (DNA)
-RNA is produced by RNA polymerases, a class of proteins that make long chains of RNA
-In ribosomes, the RNA is read and proteins are produced in extracellular organelles (ribosomes of the endoplasmic reticulum). The assembly of proteins then results in the final appearance (phenotype)
In the whole process study of the DNA can help understand overexpressed proteins,
In addition to this apparently useless microRNAs could also play an important role in the phenotype of the proteins produced. They could therfore be equally as important scientifically as the understanding of susceptibility genes.
microRNAs are RNAs NOT translated into proteins:
-their size is between 19-25 nucleotides
-more than 10000 miRNA in humans
-they regulate 30% of the coding of genes at the post-transcriptional level
-they are highly conserved in evolution
–they are necessary for functional and dysfunctional physiology of cells
*exons are coding genes in the genome (DNA). Exons comes from “expressed” in contrast to introns which are located between DNA sequences (Inter=between genes)
Source of information: Zhang XJ. Coding variants in psoriasis genetic susceptibility. Global Chinese Dermatology Summit (GCDS) Symposium. World Congress of Dermatology 2015 – Vancouver, Canada