Given a passage with a context and an answer, construct a question on the basis of the information present in the passage. Construct the question in such a way that (i) it is unambiguous, (ii) it is answerable from the passage, (iii) its answer is unique (iv) it answer uses text phrases from the passage. Avoid creating questions that (i) can't be answered correctly without actually understanding the passage and (ii) uses the same words or phrases given in the passage.

Example Input: Context: Proprotein convertase subtilisin kexin-like 9 (PCSK9) is a secreted glycoprotein that is transcriptionally regulated by cholesterol status. It modulates levels of circulating low density lipoprotein cholesterol (LDLC) by negatively regulating low density lipoprotein receptor (LDLR) levels. PCSK9 variants that result in 'gain of function' have been linked to autosomal dominant hypercholesterolemia, while significant protection from coronary artery disease has been documented in individuals who carry 'loss of function' PCSK9 variants. PCSK9 circulates in human plasma, and we previously reported that plasma PCSK9 is positively correlated with total cholesterol and LDLC in men.", 'Herein, we report the effects of two lipid-modulating therapies, namely statins and fibrates, on PCSK9 plasma levels in human subjects. We also document their effects on endogenous PCSK9 and LDLR expression in a human hepatocyte cell line, HepG2, using immunoprecipitation and immunoblot analyses. Changes in plasma PCSK9 following fenofibrate or gemfibrozil treatments (fibric acid derivatives) were inversely correlated with changes in LDLC levels (r = -0.558, p = 0.013). Atorvastatin administration (HMGCoA reductase inhibitor) significantly increased plasma PCSK9 (7.40%, p = 0.033) and these changes were inversely correlated with changes in LDLC levels (r = -0.393, p = 0.012). Immunoblot analyses of endogenous PCSK9 and LDLR expression by HepG2 cells in response to statins and fibrates showed that LDLR is more upregulated than PCSK9 by simvastatin (2.6x vs 1.5x, respectively at 10 muM), while fenofibrate did not induce changes in either.
Answer: These results suggest that in vivo (1) statins directly increase PCSK9 expression while (2) fibrates affect PCSK9 expression indirectly through its modulation of cholesterol levels and (3) that these therapies could be improved by combination with a PCSK9 inhibitor, constituting a novel hypercholesterolemic therapy, since PCSK9 was significantly upregulated by both treatments.
Example Output: Are plasma PCSK9 levels significantly modified by statins and fibrates in humans?

Example Input: Context: Recently, the Arg389Gly beta1-adrenoceptor (beta1AR) gene polymorphism has been detected. The Arg variant exhibited increased responsiveness to agonist-induced stimulation in vitro. Functional studies in isolated human atrial muscle strips and in-vivo studies revealed contradictory results regarding the functional relevance of this polymorphism. We sought to characterize the functional consequences of the Arg389Gly beta1-AR polymorphism in 30 consecutive healthy male volunteers in vivo.', 'beta1-AR genotype was determined by PCR and restriction analysis, which was confirmed by DNA sequencing. We compared heart rate, blood pressure, and contractile response of the various genotype carriers with a modified dobutamine stress echocardiography protocol.', 'Subjects homozygous for the Arg389 beta1AR showed a significantly higher increase in fractional shortening upon cumulative doses of dobutamine as compared to subjects carrying one or two copies of the Gly389 allele. A statistically significant difference was observed at a dobutamine dose of 10 microg/kg/min (46.5 +/- 1.3 vs. 41.8 +/- 1.0 %; P = 0.023) and was maximal at 40 microg/kg/min (61.9 +/- 1.4 vs. 52.8 +/- 1.6; P = 0.001). As a result, the systolic blood pressure response to dobutamine was significantly enhanced in individuals homozygous for the Arg389 allele, whereas the effect on heart rate did not differ between the two groups. Normalization for changing afterload conditions by calculating the pressure-dimension ratio revealed similar effects, indicating that the beta1AR-mediated effects are mainly a result of increased myocardial inotropy.
Answer: These data indicate that the Arg389Gly beta1AR polymorphism is functionally relevant in vivo and determines contractile responsiveness to catecholamines in humans.
Example Output: Does the Arg389Gly beta1-adrenoceptor gene polymorphism determine contractile response to catecholamines?

Example Input: Context: Chronic kidney disease (CKD) is a worldwide public health problem. It is very important to identify the factors that affect CKD. Previous studies have reported that serum bilirubin concentration was positively correlated with renal function in a cross-sectional study. The aim of this study was to investigate the relationship between serum bilirubin concentration and the progression of CKD.', 'A cohort study was performed on a consecutive series of 2784 subjects without CKD, defined as estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m(2), at baseline. We analyzed the relationship between serum total bilirubin concentration at baseline and new-onset CKD in the general population.', 'We followed the subjects for a median period of 7.7 years. There were 1157 females and 1627 males, and 231 females and 370 males developed CKD during this period. Multiple Cox regression analyses revealed that serum total bilirubin concentration (hazard ratio (HR) per 1.0 mol/L increase 0.97 (95% CI 0.95-0.99), P = 0.0084) in addition to age, gamma-glutamyl transpeptidase (GGT), uric acid (UA), creatinine and medication for hypertension in men and serum total bilirubin concentration (HR per 1.0 mol/L increase 0.96 (95% CI 0.93-1.00), P = 0.0309) in addition to age, GGT, alanine aminotransferase, UA, creatinine and medication for dyslipidemia in women were independent predictors of new-onset CKD, after adjusting for confounders.
Answer: Our study demonstrated that serum total bilirubin concentration could be a novel risk factor for the progression of CKD, defined as eGFR <60 ml/min/1.73 m(2), in the general population.
Example Output:
Is low serum bilirubin concentration a predictor of chronic kidney disease?