title: Interactions of central obesity with rs3918242 on risk of non-alcoholic fat liver disease: a preliminary case-control study.
abstract: NAFLD is a complex disease characterized by inflammation and insulin resistance which is determined by an interaction of genetics and environmental factors. MMP gene has been implicated in relation to inflammation and insulin resistance. The preliminary case-control study aimed to investigate the association between Matrix metalloproteinase (MMP)-9-1562C/T (rs3918242), MMP-2-1306C/T (rs243865) and risk of NAFLD and to further evaluate the interactions of central obesity with rs3918242 and rs243865. Two variants, rs3918242 and rs243865, were genotyped by polymerase chain reaction -restriction fragment length polymorphism. Gene-environment interactions on risk of NAFLD was preliminarily investigated by generalized multifactor dimensionality reduction (GMDR) and further confirmed by unconditional logistic regression methods. After adjusting for covariates, increased risk of NAFLD were observed in subjects carrying TT/CT genotypes in rs3918242 ((Adjust)OR=1.64, 95% CI: 1.24, 2.11, P=0.006). However, decreased risk of non-alcoholic fat liver disease was found when MMP-2 rs243865 (TT/CT) genotype carriers compared with CC carrier ((Adjust)OR=0.65, 95% CI: 0.47, 0.72, P=0.000).Interactions of central obesity with rs3918242 was preliminarily found by GMDR, with a maximum prediction accuracy (67.61%) and a maximum Cross-validation Consistency (10/10).The unconditional logistic regression method indicated central obesity-positive subject with genotype TT/CT had 4.54 times risk of NAFLD compared to central obesity-negative subjects with genotype CC (OR(add)(a)=4.54, 95% CI: 2.81, 7.21, P(add)(a)=0.000), which further confirmed the interactions. The results indicate that both rs3918242 and rs243865 is associated with risk of NAFLD. Furthermore, rs3918242 and central obesity have synergistic effects on risk of NAFLD.
authors.affiliation: De partment of Gastroenterology, Renmin Hospital of Wuhan University 238 Jiefang Road, Wuhan, China.
authors.forename: Pengbo
authors.initials: P
authors.lastname: Wu
authors.affiliation: Department of Gastroenterology, Renmin Hospital of Tongcheng Minzhu Road 120, Hubei, China.
authors.forename: Yonglong
authors.initials: Y
authors.lastname: Hua
authors.affiliation: De partment of Gastroenterology, Renmin Hospital of Wuhan University 238 Jiefang Road, Wuhan, China.
authors.forename: Shiyun
authors.initials: S
authors.lastname: Tan
authors.affiliation: De partment of Gastroenterology, Renmin Hospital of Wuhan University 238 Jiefang Road, Wuhan, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.affiliation: De partment of Gastroenterology, Renmin Hospital of Wuhan University 238 Jiefang Road, Wuhan, China.
authors.forename: Yongxiang
authors.initials: Y
authors.lastname: Shu
authors.affiliation: De partment of Gastroenterology, Renmin Hospital of Wuhan University 238 Jiefang Road, Wuhan, China.
authors.forename: Guo
authors.initials: G
authors.lastname: Fang
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005260:Female; D005787:Gene Frequency; D059647:Gene-Environment Interaction; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D016015:Logistic Models; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics*; D008875:Middle Aged; D015999:Multivariate Analysis; D065626:Non-alcoholic Fatty Liver Disease / Q000175:diagnosis / Q000235:genetics*; D056128:Obesity, Abdominal / Q000150:complications* / Q000175:diagnosis; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: Interactions; central obesity; matrix metalloproteinase; non-alcoholic fat liver disease; polymorphisms