Association of a genetic polymorphism in ectonucleotide pyrophosphatase/phosphodiesterase 1 with hepatitis C virus infection and hepatitis C virus core antigen levels in subjects in a hyperendemic area of Japan.
BACKGROUND
The clinical course of chronic hepatitis C virus (HCV) infection is strongly associated with insulin resistance and obesity. The K121Q polymorphism in the ectonucleotide pyrophosphatase/phosphodiesterase (ENPP)-1 gene and the rs7566605 genotype located near insulin-induced gene 2 have been shown to be associated with insulin resistance and obesity. This study examined whether the K121Q polymorphism in ENPP1 or the rs7566605 genotype is associated with the clinical course of HCV infection.


METHODS
The relationships between the clinical characteristics of 469 anti-HCV antibody-seropositive subjects (353 were positive for HCV core antigen or RNA, whereas 116 were negative for HCV RNA) and the polymorphisms were analyzed.


RESULTS
No significant differences in body mass index, plasma glucose level, serum insulin level, and other biochemical markers were observed between subgroups of subjects with different genotypes at the K121Q polymorphism or rs7566605. The frequency of the homozygous wild-type genotype at K121Q in HCV carriers, however, was significantly higher than that in subjects who were negative for HCV RNA (84.5% vs. 75.9%; P < 0.05). Moreover, in HCV carriers, HCV core antigen levels in subjects homozygous for the wild-type genotype at K121Q were significantly higher than in heterozygous carriers of K121Q (5358 fmol/l vs. 4002 fmol/l; P = 0.04). In contrast, the rs7566605 genotype was not associated with hepatitis C viremia or with the HCV core antigen level.


CONCLUSIONS
The K121Q variant of ENPP1 may be associated with hepatitis C viremia and core antigen levels in HCV carriers.
Takahama
Yuka
Y
Miyazaki Prefectural Industrial Support Foundation, Miyazaki, Japan.
Uto
Hirofumi
H
Kanmura
Shuji
S
Oketani
Makoto
M
Ido
Akio
A
Kusumoto
Kazunori
K
Hasuike
Satoru
S
Nagata
Kenji
K
Hayashi
Katsuhiro
K
Stuver
Sherri
S
Okayama
Akihiko
A
Tsubouchi
Hirohito
H
D000368:Aged; D000369:Aged, 80 and over; D001786:Blood Glucose / Q000502:physiology; D015992:Body Mass Index; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D006526:Hepatitis C / Q000453:epidemiology / Q000235:genetics*; D018936:Hepatitis C Antigens / Q000097:blood / Q000235:genetics*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007328:Insulin / Q000097:blood; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D010727:Phosphoric Diester Hydrolases / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011755:Pyrophosphatases / Q000235:genetics*; D014766:Viremia
D001786:Blood Glucose; D018936:Hepatitis C Antigens; D007328:Insulin; D010727:Phosphoric Diester Hydrolases; C065962:ectonucleotide pyrophosphatase phosphodiesterase 1; D011755:Pyrophosphatases