Genetic polymorphims in promoter region of osteopontin gene may be a marker reflecting hepatitis activity in chronic hepatitis C patients.
OBJECTIVE
Osteopontin, an extracellular matrix protein with RGD motif, is shown to be a cytokine essential for Th1 immune response initiation. Genetic polymorphisms in the osteopontin gene (OPN) determine the magnitude of immunity against rickettsial infection in mice. Similar polymorphisms, if present also in human beings, might affect hepatitis activity in those infected with HCV.


METHODS
Blood was collected from 176 patients with chronic hepatitis C. SNPs in the promoter region of OPN were analyzed in 20 patients by direct sequencing of DNA fragments amplified by PCR and in 156 patients by Invader assay. Ninety-five patients compatible to evaluation criteria were classified into three groups depending on maximal serum ALT levels during the observation periods at least for 2 years as follows; lower than 30IU/L (low-activity group), between 30 and 80IU/L with no hepatoprotective treatment (medium-activity group), and higher than 80IU/L irrespective of hepatoprotective treatment (high-activity group).


RESULTS
There were 16, 19, and 60 patients in the low-, medium-, and high-activity groups, respectively. Four SNPs (nt -155, -443, -616, and -1748) were detected in the promoter region of OPN. Among them, the SNP at nt -443 (C or T) was a novel one and showed an association with hepatitis activity in our patients: T/T homozygosity was found in 2 (13%), 8 (42%), and 25 (44%), and C/T heterozygosity in 12 (75%), 8 (42%), and 23 (40%), in the low-, medium-, and high-activity groups, respectively. The other 3 SNPs already known showed linkage disequilibrium with D(') and r(2) greater than 0.937 to each other without correlation to disease activity.


CONCLUSIONS
OPN promoter region SNP at nt -433 may be a useful marker reflecting hepatitis activity in chronic hepatitis C patients.
Mochida
Satoshi
S
Gastroenterology and Hepatology (Third Department of Internal Medicine), Saitama Medical School, Saitama, Japan.
Hashimoto
Michie
M
Matsui
Atsushi
A
Naito
Masashi
M
Inao
Mie
M
Nagoshi
Sumiko
S
Nagano
Makoto
M
Egashira
Tohru
T
Mishiro
Shunji
S
Fujiwara
Kenji
K
D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000235:genetics; D005260:Female; D005819:Genetic Markers; D019698:Hepatitis C, Chronic / Q000201:enzymology / Q000235:genetics*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D053495:Osteopontin; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012795:Sialoglycoproteins / Q000235:genetics*
D005819:Genetic Markers; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; C506896:Spp1 protein, mouse; D053495:Osteopontin; D004247:DNA; D000410:Alanine Transaminase