ATP binding cassette G8 T400K polymorphism may affect the risk of gallstone disease among Chinese males.
BACKGROUND
Supersaturation of bile with cholesterol is a primary step in the formation of cholesterol gallstones. ATP binding cassette (ABC) G5 and G8 play an important role in regulating sterol absorption and secretion. To investigate a possible association between transporter gene polymorphism and gallstone formation, we examined five common polymorphisms in the ABCG5 (Q604E) and ABCG8 (D19H, Y54C, T400K, A632V) genes in patients with gallstone disease (GS).


METHODS
Study subjects included 287 patients with GS and 219 gallstone free controls (GSF). Polymorphisms were determined using PCR-RFLP analysis or the Taqman MGB assay. Plasma and biliary lipid levels were measured.


RESULTS
2 SNPs of ABCG8 gene (Y54C and T400K) showed strong linkage disequilibrium (D'=0.824, r2=0.579). Male carriers of the less frequent K allele of ABCG8 T400K had a 2.31-fold elevated risk [95% confidence interval (CI) 1.12 approximately 4.76, P=0.023] for gallstone disease compared to male with the common genotype after the adjustment for age, body mass index. Males with the K allele had lower plasma triglyceride (P=0.044) and biliary phospholipid (P=0.035) levels than TT homozygotes. No such association was found in female or other 4 SNPs.


CONCLUSIONS
These findings indicate that the T400K polymorphism in ABCG8 may be associated with the incidence of gallstone disease in males.
Wang
Yong
Y
Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Ruijin er Road, Shanghai 200025, China.
Jiang
Zhao-Yan
ZY
Fei
Jian
J
Xin
Lin
L
Cai
Qu
Q
Jiang
Zhi-Hong
ZH
Zhu
Zheng-Gang
ZG
Han
Tian-Quan
TQ
Zhang
Sheng-Dao
SD
D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D019943:Amino Acid Substitution; D044466:Asian People / Q000235:genetics; D002681:China; D005260:Female; D042882:Gallstones / Q000235:genetics*; D005787:Gene Frequency; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008055:Lipids / Q000097:blood; D008239:Lysine / Q000737:chemistry / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012306:Risk; D012737:Sex Factors; D013912:Threonine / Q000737:chemistry / Q000235:genetics
C416946:ABCG8 protein, human; D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters; D008055:Lipids; D013912:Threonine; D008239:Lysine