Association between angiotensin II type 1 receptor polymorphisms and the occurrence of nonalcoholic fatty liver disease.
BACKGROUND
Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver injury in many countries. Genetic factors are important for the development of NAFLD, as well as environmental factors. Recently an angiotensin II type 1 receptor (AGTR1) has been recognized as important in the aetiology of fibrosis in the liver.


OBJECTIVE
In this study we investigated the association between angiotensin II type 1 receptor gene polymorphism (ATGR1) and NAFLD.


METHODS
One hundred and sixty-seven NAFLD patients [106 with nonalcoholic steatohepatitis (NASH) and 61 with simple steatosis] with a positive diagnosis by liver biopsy and 435 healthy control subjects were recruited in this study.


RESULTS
We investigated 12 single nucleotide polymorphisms (SNPs) of the ATGR1 gene, among which rs3772622 showed the lowest P-value of allele frequency model (P=0.0000012) with an odds ratio (95% confidence interval) of 1.95 (1.49-2.55). Five SNPs (rs3772622, rs3772633, rs2276736, rs3772630 and rs3772627) were significantly associated with NAFLD, even when the most conservative Bonferroni's correction was applied. Linkage disequilibrium analysis revealed that SNP rs3772622 and another four SNPs (rs3772633, rs2276736, rs3772630 and rs3772627) were in the same block. We investigated the association between rs3772622 genotypes and the fibrosis index. The results of the analysis revealed an additive increase of the fibrosis index in the patients with the A allele of rs3772622.


CONCLUSIONS
This is the first report to demonstrate the genetic variations in ATGR1 that may influence the risk of NAFLD and liver fibrosis in NAFLD.
Yoneda
Masato
M
Division of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama City University Hospital, Yokohama, Japan.
Hotta
Kikuko
K
Nozaki
Yuichi
Y
Endo
Hiroki
H
Uchiyama
Takashi
T
Mawatari
Hironori
H
Iida
Hiroshi
H
Kato
Shingo
S
Fujita
Koji
K
Takahashi
Hirokazu
H
Kirikoshi
Hiroyuki
H
Kobayashi
Noritoshi
N
Inamori
Masahiko
M
Abe
Yasunobu
Y
Kubota
Kensuke
K
Saito
Satoru
S
Maeyama
Shiro
S
Wada
Koichiro
K
Nakajima
Atsushi
A
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D018450:Disease Progression; D005234:Fatty Liver / Q000235:genetics* / Q000473:pathology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007564:Japan; D015810:Linkage Disequilibrium; D008103:Liver Cirrhosis / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics*; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index
D044140:Receptor, Angiotensin, Type 1