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Genetic Variants in the SAMM50 Gene Create Susceptibility to Nonalcoholic Fatty Liver Disease in a Chinese Han Population.

Chen L, Lin Z, Jiang M, Lu L, Zhang H, Xin Y, Jiang X, Xuan S - Hepat Mon (2015)

Bottom Line: The SNP-SNP interactions were analyzed by performing multifactor dimensionality reduction (MDR) and generalized multifactor dimensionality reduction (GMDR).Moreover, the rs738491 T allele carriers had significantly higher levels of alanine aminotransferase (ALT) (P = 0.017) than did the noncarriers.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).

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China.

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).

Objectives: The present study evaluated the association between the three genetic variants in the SAMM50 gene and susceptibility to NAFLD in a Chinese Han population.

Patients and 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.

No MeSH data available.


Related in: MedlinePlus

SNP-SNP Interaction DendrogramThe shorter the line connecting the 2 SNPs, the stronger the interaction. Green and blue represent redundancy or correlation.
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fig23135: SNP-SNP Interaction DendrogramThe shorter the line connecting the 2 SNPs, the stronger the interaction. Green and blue represent redundancy or correlation.

Mentions: As is shown in Figures 1 and 2, the dendrogram and the Fruchterman-Reingold described the interactions between these SNPs. The results of the GMDR model analysis of the SNP-SNP interactions are demonstrated in Table 5. The results showed that rs2143571 was the best single-locus model to predict NAFLD (testing accuracy [TA], 54.94%; P = 0.0547; cross-validation consistency [CVC], 8/10). The best two-locus model was the combination of rs2143571 and rs3761472 (TA, 62.21%; P = 0.001; CVC, 10/10). The three-locus model included rs738491, rs2143571, and rs3761472 (TA, 60.79%; P = 0.001; CVC, 10/10). Therefore, the best model was the two-locus model, a combination of rs2143571 and rs3761472, with the highest TA and perfect CVC (OR, 2.9430; 95%CI, 1.9291 to 4.4899; P < 0.0001).


Genetic Variants in the SAMM50 Gene Create Susceptibility to Nonalcoholic Fatty Liver Disease in a Chinese Han Population.

Chen L, Lin Z, Jiang M, Lu L, Zhang H, Xin Y, Jiang X, Xuan S - Hepat Mon (2015)

SNP-SNP Interaction DendrogramThe shorter the line connecting the 2 SNPs, the stronger the interaction. Green and blue represent redundancy or correlation.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4644533&req=5

fig23135: SNP-SNP Interaction DendrogramThe shorter the line connecting the 2 SNPs, the stronger the interaction. Green and blue represent redundancy or correlation.
Mentions: As is shown in Figures 1 and 2, the dendrogram and the Fruchterman-Reingold described the interactions between these SNPs. The results of the GMDR model analysis of the SNP-SNP interactions are demonstrated in Table 5. The results showed that rs2143571 was the best single-locus model to predict NAFLD (testing accuracy [TA], 54.94%; P = 0.0547; cross-validation consistency [CVC], 8/10). The best two-locus model was the combination of rs2143571 and rs3761472 (TA, 62.21%; P = 0.001; CVC, 10/10). The three-locus model included rs738491, rs2143571, and rs3761472 (TA, 60.79%; P = 0.001; CVC, 10/10). Therefore, the best model was the two-locus model, a combination of rs2143571 and rs3761472, with the highest TA and perfect CVC (OR, 2.9430; 95%CI, 1.9291 to 4.4899; P < 0.0001).

Bottom Line: The SNP-SNP interactions were analyzed by performing multifactor dimensionality reduction (MDR) and generalized multifactor dimensionality reduction (GMDR).Moreover, the rs738491 T allele carriers had significantly higher levels of alanine aminotransferase (ALT) (P = 0.017) than did the noncarriers.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).

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China.

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).

Objectives: The present study evaluated the association between the three genetic variants in the SAMM50 gene and susceptibility to NAFLD in a Chinese Han population.

Patients and 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.

No MeSH data available.


Related in: MedlinePlus