ABSTRACT
<p><b>BACKGROUND</b>Many studies have suggested that cigarette smoking and polymorphisms of resistin and glutathione peroxidase-1 (GPx-1) genes are closely correlated with the pathogenesis of nonalcoholic fatty liver disease (NAFLD). However, few reports have investigated these associations with respect to NAFLD susceptibility. We, therefore, examined the distribution of polymorphisms in GPx-1 and resistin genes in NAFLD patients and healthy controls and analyzed the relationship between these polymorphisms and smoking status.</p><p><b>METHODS</b>Nine hundred NAFLD patients and 900 healthy controls were selected, and the genetic polymorphisms of resistin gene promoter-420C/G and GPx-1 gene Pro198Leu were analyzed by polymorphism-polymerase chain reaction (PCR) in DNA extracted from peripheral blood leukocytes. Interactions between the two mutants and the gene-environment interaction with cigarette smoking were also analyzed.</p><p><b>RESULTS</b>Genotype frequencies of -420C/G (GG) and Pro198Leu (LL) were significantly higher in NAFLD cases (49.56% and 50.11%, respectively) compared with healthy controls (23.67% and 24.22%, respectively) (P = 0.0069; P = 0.0072). Moreover, the risk of NAFLD with -420C/G (GG) was significantly higher than in controls (odds ratio [OR] =3.1685, 95% confidence interval (CI) =1.9366-5.2073). Individuals carrying Pro198Leu (LL) had a high risk of NAFLD (OR = 3.1424, 95% CI = 1.7951-5.2367). Combined analysis of the polymorphisms showed that the -420C/G (GG)/Pro198Leu (LL) genotype was significantly more common in the NAFLD group than in the control group (39.44% vs. 12.78%, respectively, P = 0.0054), while individuals with -420C/G (GG)/Pro198Leu (LL) had a high risk of NAFLD (OR = 5.0357, 95% CI = 3.1852-7.8106). Moreover, the cigarette smoking rate in the NAFLD group was significantly higher than in the control group (OR = 1.8990, P = 0.0083 in the smoking index (SI) ≤400 subgroup; OR = 5.0937, P = 0.0051 in the SI >400 subgroup), and statistical analysis suggested a positive interaction between cigarette smoking and -420C/G (GG) (γ = 5.6018 in the SI ≤400 subgroup; γ = 4.4770 in the SI >400 subgroup) and Pro198Leu (LL) (γ = 5.7715 in the SI ≤400 subgroup; γ = 4.5985 in the SI >400 subgroup) in increasing the risk of NAFLD.</p><p><b>CONCLUSION</b>NAFLD risk factors include -420C/G (GG), Pro198Leu (LL) and cigarette smoking, and these three factors have a significant additive effect on NAFLD risk.</p>
Subject(s)
Female , Humans , Male , Genetic Predisposition to Disease , Genetics , Glutathione Peroxidase , Genetics , Non-alcoholic Fatty Liver Disease , Metabolism , Polymorphism, Single Nucleotide , Genetics , Promoter Regions, Genetic , Genetics , Resistin , Genetics , Smoking , GeneticsABSTRACT
This study is to investigate the influence and the expression of CMTM family of testosterone on spermatogenesis suppression in the male rats treated by gossypol and cyclophosphamide. Gossypol (50 mg kg(-1)) and cyclophosphamide (20 mg kg(-1)) were administered to male rats to induce spermatogenesis suppression. Testosterone propionate was administrated at the dose of 5 mg kg(-1) every other day for 6 times. Sperm was collected from the left caudal epididymis, the count and motility of sperm were analyzed by CASA. Morphological change of testis tissue was observed with HE staining. The expression of CMTM family was examined by Western blotting assay. Gossypol (50 mg kg(-1)) and cyclophosphamide (20 mg kg(-1)) decreased the count and motility of sperm, and the pathological change of testis tissue was also observed. But, testosterone (5 mg kg(-1)) had positive effect. Furthermore, CMTM4 down-expressed remarkably in the gossypol and cyclophosphamide treated rats, the expression of the CMTM4 was up-expressed after testosterone administration. On the contrary, the expression of CMTM2 increased significantly only in gossypol treated male rats, but not in cyclophosphamide treated male rats. The expression of CMTM2 was down-expressed after testosterone administration. However, no obvious change of CMTM2 was observed in cyclophosphamide treated rats. Testosterone did not influence the expression of CKLF1, CMTM3 and CMTM5, the CMTM6, CMTM7 and CMTM8 of CMTM family were not detected in testis tissue. These demonstrated that the spermatogenesis effect of testosterone (5 mg kg(-1)) was associated with the expression of CMTM family, and CMTM2 and CMTM4 may take part in the spermatogenesis process.