ABSTRACT
AIM: Apolipoprotein AV (APOA5) is an important determinant of plasma triglyceride concentration. This study aimed to investigate the relationship of an amino acid substitution at position 182 (G182C) of the apolipoprotein AV (APOA5) gene with triglyceride concentration in a Taiwanese population. METHODS: This study enrolled two cohorts: non-diabetic subjects (112 males and 89 females) aged 50.3+/-11.0 years (mean+/-sd) and diabetic subjects (106 males and 96 females) aged 62.1+/-10.3 years. The relationship between the G182C polymorphism (rs 2075291) and plasma triglycerides was examined. Demographic and metabolic parameters including age, sex, body mass index, fasting plasma glucose and total cholesterol were also obtained. RESULTS: The G182C polymorphism was a determinant of plasma triglycerides in both non-diabetic (P=0.022) and diabetic (P=0.003) groups, independent of age, gender, fasting plasma glucose, body mass index and total cholesterol. In the diabetic group, this genetic polymorphism interacts significantly (P=0.032) with fasting plasma glucose concentration on plasma triglycerides after adjustment for age, sex, body mass index and total cholesterol. CONCLUSIONS: In conclusion, the G182C polymorphism of the APOA5 gene affects plasma triglycerides in both non-diabetic and diabetic populations. The observed interaction of gene and glycaemic control further indicates a multifactorial nature of clinical phenotypes in subjects with Type 2 diabetes.
Subject(s)
Apolipoproteins/genetics , Diabetes Mellitus, Type 2/genetics , Polymorphism, Single Nucleotide/genetics , Triglycerides/blood , Adult , Aged , Apolipoprotein A-V , Apolipoproteins A , Cohort Studies , Female , Genetic Predisposition to Disease , Humans , Male , Middle Aged , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , TaiwanABSTRACT
Translational control is one of the mechanisms that regulate thymidine kinase (TK) expression in the cell cycle. Evidence for the TK mRNA sequence that is involved in its own translation has been lacking. In this report, we show that TK-deficient mouse fibroblasts transfected with pFLAG-TK express a TK mRNA containing the 5'-untranslated region (5'UTR) and produce two polypeptides, FLAG-TK and TK, resulting from an alternative initiation of translation. Most interestingly, the 5'UTR of TK allowed the translation of FLAG-TK mRNA to become cap-independent in an in vitro translation system. Furthermore, this 5'UTR sequence decreased significantly the efficiency of translation from the AUG codon of FLAG when the concentration of FLAG-TK RNA was low. Here, we also show that in normal human IMR-90 fibroblasts the induction of TK polypeptide by serum stimulation is insensitive to rapamycin treatment, which is known to inhibit the translations of transcripts of some growth-controlled genes by affecting the cap-binding efficiency. Taken together, we propose that the 5'UTR in TK mRNA might actually confer a secondary structure to regulate ribosome binding during translation in a cap-independent manner.
