ABSTRACT
PURPOSE OF THE REVIEW: To summarize current knowledge on interactions between genetic variants and lifestyle factors (G×L) associated with the development of coronary artery disease (CAD) and prioritize future research. RECENT FINDINGS: Genetic risk and combined lifestyle factors and behaviors have a log-additive effect on the risk of developing CAD. First, we describe genetic and lifestyle factors associated with CAD and then focus on G×L interactions. The majority of G×L interaction studies are small-scale candidate gene studies that lack replication and therefore provide spurious results. Only a few studies, of which most use genetic risk scores or genome-wide approaches to test interactions, are robust in number and analysis strategy. These studies provide evidence for the existence of G×L interactions in the development of CAD. Further G×L interactions studies are important as they contribute to our understanding of disease pathophysiology and possibly provide insights for improving interventions or personalized recommendations.
Subject(s)
Coronary Artery Disease/genetics , Gene-Environment Interaction , Life Style , Coronary Artery Disease/etiology , Coronary Artery Disease/physiopathology , Genetic Predisposition to Disease , Genome-Wide Association Study , Humans , Polymorphism, Single Nucleotide , Risk FactorsABSTRACT
The dopamine D2 receptor encoded by DRD2 has been implicated in multiple psychiatric disorders, mediated at least in part by two intronic variants affecting mRNA splicing, rs1076560 and rs2283265, and a less frequent enhancer variant, rs12364283, which increases DRD2 mRNA expression. This study tests whether these functionally validated variants confer susceptibility toward heroin addiction in a Pakistani population. A total of 540 heroin addicts and 467 healthy controls were genotyped, basic allele and genotype tests were performed. Neither rs1076560 nor rs2283265 significantly associated with heroin addiction. The enhancer rs12364283 occurs more frequently in heroin-dependent cases than controls (MAF 13% vs. 7%, respectively), revealing significant association with heroin addiction (p = 3.0E-06, OR 2.1). This study identifies rs12364283 of DRD2 as a potential risk factor for heroin addiction in the Pakistani study population. This enhancer variant had been shown to increase DRD2 mRNA expression, a possible factor in increased vulnerability to heroin addiction. Further studies are needed to validate this association of rs12364283.
Subject(s)
Enhancer Elements, Genetic , Heroin Dependence/genetics , Receptors, Dopamine D2/genetics , Case-Control Studies , Gene Frequency , Genotype , Humans , PakistanABSTRACT
OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) has emerged in the last two decades with worldwide prevalence of 25.24%. Due to its increasing frequency in Pakistan, it was aimed to identify disease predisposing metabolic risks and their association with NAFLD. METHODS: Anthropometric and biochemical investigations were collected from 1366 subjects with minor metabolic disturbances. Comparative analyses were performed to compute frequencies of common metabolic risk phenotypes while their associations with NAFLD were explored using regression analyses. The prevalence of NAFLD was also estimated in total, age, and gender-based population cohorts. RESULTS: Among metabolic risk phenotypes obesity, hyperglycemia, hypertension, and dyslipidemia significantly associated (p<0.001) with NAFLD risk irrespective of age, gender, and BMI. Prevalence of NAFLD in total study cohort was 14.8%, 16.1% in males, 13.4% in females, 19.9% in ≥40 years and 8.7% in ≤40 years respectively. CONCLUSION: General Pakistani populations experiencing common metabolic disturbances are at high risk of NAFLD development, especially male gender and advanced age. Based on these parameters the stratified NAFLD population could be treated accordingly.
