Fibrosis susceptibility gene and uses thereof
a fibrosis susceptibility and gene technology, applied in the field of genetics and medicine, can solve the problems of inability to identify a good marker allowing to predict and follow the progression of hepatic fibrosis in schistosome infected subjects, and inability to afford a global assessment of hepatic fibrosis
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example 1
Association Between SNPs in the CTGF Gene Locus with Severe Hepatic Fibrosis (HF) in Two Chinese Populations' Samples
[0095]Data are provided for two independent Chinese samples (fishermen and farmers living in region endemic for S. japonicum). Disease phenotype included advanced hepatic fibrosis (fishermen) as described in Materials and Methods, or ascites and previous bleedings (farmers).
[0096]Association between genotypes and hepatic fibrosis (HF) phenotypes (described in Material and Methods) have been tested first using univariate analysis (upper part of the Table 4) and second by multivariate analysis (lower part of the Table 4) including SNPs or alterations rs12526196, rs1931002, rs3037970 and rs9402373 that showed the strongest associations when tested again SNPs from the same bin. Bins are correlation (r2>0.5) groups, genotype is the aggravating genotype, OR=Odd ratios, CI=Confidence interval of OR.
[0097]Fisherman sample: n=300, 99 cases and 201 controls; covariates: number ...
example 2
Association Between SNPs in the CTGF Gene Locus with Severe Hepatic Fibrosis (HF) in Sudaneses and Brazilians Infected with Schistosoma Mansoni
[0105]The two principal schistosome strains that cause HF are S. japonicum in Asia, and S. mansoni in Africa and in South America. We have investigated whether HF in S. mansoni endemic region of Sudan and Brazil was also affected by CTGF allelic variants. CTGF polymorphisms that were associated with HF in Chinese fishermen (Table 4) were genotyped in both samples. The phenotypes were either severe HF associated with portal hypertension in Sudanese or significant secondary portal branch thickening in Brazilians who were much less affected than Sudanese since transmission was lower in the Brazilians than in the Sudanese sample.
[0106]Associations between genotypes and HF phenotypes (described in Materials and Methods) have been tested first using univariate analysis (upper part of Table 5) and second by multivariate analysis (lower part of Tabl...
example 3
Association Between SNPs in the CTGF Gene Locus with Hepatic Fibrosis (HF) in HCV Infected Subjects
[0118]Analysis of CTGF Genetic Variants in French Subjects Infected with HCV.
[0119]Example 1 describes SNP correlation bins (r2>0.8) in the CTGF encoding gene in a sample of Chinese population. These were defined over the entire gene and 10 Kb of the 3′ and 5′ flanking region. Only SNPs with a minor allele frequency>20% had been analyzed. There were seven bins of which four (groups II, III, IV and VI) showed some association with hepatic fibrosis caused by schistosome eggs in Chinese fishermen infected by Schistosoma japonicum. In Example 3, the inventors genotyped two SNPs in each of these four bins and an additional SNP rs9399005 (that showed suggestive associations with schistosomal fibrosis) in a French sample infected with HCV and determined whether any of them were associated with advanced hepatic fibrosis. They found evidence for association in bins III and VI but not in bins II...
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