title: Genetic Variants in the SAMM50 Gene Create Susceptibility to Nonalcoholic Fatty Liver Disease in a Chinese Han Population.
abstract: BACKGROUND
  Genome-wide association studies have shown that rs738491, rs2143571, and rs3761472 in the sorting and assembly machinery component 50 homolog (SAMM50) gene are significantly associated with susceptibility to nonalcoholic fatty liver disease (NAFLD).
  
  
  OBJECTIVE
  The present study evaluated the association between the three genetic variants in the SAMM50 gene and susceptibility to NAFLD in a Chinese Han population.
  
  
  METHODS
  Genotypes for 3 single nucleotide polymorphisms (SNPs), viz rs738491, rs2143571, and rs3761472, in the SAMM50 gene were determined using an improved multiplex ligation detection reaction technique in 340 B-type ultrasonography-diagnosed NAFLD patients and 452 healthy controls. Meanwhile, serum lipid profiles and liver enzymes were estimated using standard clinical laboratory methods. The SNP-SNP interactions were analyzed by performing multifactor dimensionality reduction (MDR) and generalized multifactor dimensionality reduction (GMDR).
  
  
  RESULTS
  The genotype and allele frequencies of the SAMM50 polymorphisms between the NAFLD group and the control group were significantly different (all Ps < 0.05). In the multivariate analysis adjusted for gender, age, and body mass index, the carriers of the rs738491 T allele, rs2143571 A allele, and rs3761472 G allele had significantly increased susceptibility to NAFLD (OR, 1.507; 95% CI, 1.035 to 2.195; P = 0.032; OR, 1.761; 95% CI, 1.232 to 2.517; P = 0.002; OR, 1.483; 95% CI, 1.039 to 2.115; P = 0.030, respectively). Moreover, the rs738491 T allele carriers had significantly higher levels of alanine aminotransferase (ALT) (P = 0.017) than did the noncarriers. However, differences in the levels of serum triglyceride (TG) and aspartate aminotransferase (AST) were not statistically significant (P = 0.123; P = 0.107). The Rs2143571 A allele and the rs3761472 G allele were both deeply associated with increased levels of serum TG, ALT, and AST (all Ps < 0.05). Furthermore, the MDR and GMDR showed that a synergistic relationship might exist between rs738491, rs2143571, and rs3761472 in the SAMM50 gene and the pathophysiology and genetics of NAFLD.
  
  
  CONCLUSIONS
  We first demonstrated that the rs738491 T allele, rs2143571 A allele, and rs3761472 G allele in the SAMM50 gene created susceptibility to NAFLD in a Chinese Han population. The combination of the three SNPs in the SAMM50 gene may have synergism to predict the predisposition to NAFLD.
authors.affiliation: Department of Gastroenterology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China.
authors.forename: Lizhen
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China.
authors.forename: Zhonghua
authors.initials: Z
authors.lastname: Lin
authors.affiliation: Department of Gastroenterology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China.
authors.forename: Man
authors.initials: M
authors.lastname: Jiang
authors.affiliation: Central Laboratories, Qingdao Municipal Hospital, Qingdao, China.
authors.forename: Linlin
authors.initials: L
authors.lastname: Lu
authors.affiliation: Department of Gastroenterology, Qingdao Central Hospital, Qingdao, China.
authors.forename: Haiying
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China.
authors.forename: Yongning
authors.initials: Y
authors.lastname: Xin
authors.affiliation: Department of Gastroenterology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China.
authors.forename: Xiangjun
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Department of Gastroenterology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China.
authors.forename: Shiying
authors.initials: S
authors.lastname: Xuan
keywords: Nonalcoholic Fatty Liver Disease; Polymorphism; SAMM50; Single Nucleotide