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.

[EX Q]: Context: The single nucleotide polymorphism rs10494366 in the nitric oxide synthase 1 adaptor protein (NOS1AP) gene is associated with QTc prolongation, through an effect on the intracellular Ca levels. As sulfonylurea stimulate insulin secretion by an increased influx of Ca, we hypothesized that this polymorphism is associated with the glucose-lowering effect and mortality risk in sulfonylurea users.', 'Associations between the NOS1AP polymorphism, prescribed doses, and mortality rates in sulfonylurea, metformin, and insulin users were assessed in the Rotterdam Study, a population-based cohort study of 7983 elderly people.', 'We identified 619 participants who were prescribed oral antidiabetic drugs during follow-up. In glibenclamide users carrying the TG genotype, the prescribed doses were higher compared with the glibenclamide users carrying the TT genotype [0.38 defined daily dose units, 95% confidence interval (CI) 0.14-0.63]. Glibenclamide users with the TG or GG genotype had an increased mortality risk compared with glibenclamide users with the TT genotype [hazard ratio (HR) 2.80, 95% CI: 1.09-7.22]. Tolbutamide users with the TG or GG genotype (HR: 0.30, 95% CI: 0.14-0.63) and glimepiride users with the TG or GG genotype (HR: 0.18, 95% CI: 0.04-0.74) had a decreased mortality risk compared with tolbutamide and glimepiride users with the TT genotype.
Answer: In participants with the TG or GG genotype at rs10494366 in the NOS1AP gene, glibenclamide is less effective in reducing glucose levels and mortality rates were higher compared with glibenclamide users with the TT genotype. In tolbutamide and glimepiride users, the TG and GG genotype were associated with a reduced mortality rate.
[EX A]: Is common variation in the NOS1AP gene associated with reduced glucose-lowering effect and with increased mortality in users of sulfonylurea?

[EX Q]: Context: Impaired endothelial function, as assessed by brachial artery flow-mediated dilation (FMD), is an established risk factor for cardiovascular events. FMD is impaired in heart failure (HF) patients, but less is known about hyperemic brachial artery flow. We investigated the relationship between FMD and hyperemic flow with adverse clinical outcomes in HF patients.', 'Brachial artery FMD and hyperemic flow were assessed in 156 patients (70.5 % Male; 45.5% Caucasian; mean age (± SD) = 56.2 (±12.4) years) with HF and reduced left ventricular ejection fraction (LVEF). Cox proportional hazard models were used to assess the potential explanatory association of FMD and hyperemic flow with the composite outcome of death or cardiovascular hospitalization over a median 5-year follow-up period.', 'Both FMD and hyperemic flow were negatively correlated with age, but unrelated to sex, race, body mass index, LVEF or N-terminal pro-B-Type natriuretic peptide (NT-ProBNP). Reduced hyperemic flow, but not FMD, was associated with an increased risk of death or cardiac hospitalization after controlling for traditional risk factors.
Answer: The association of reduced hyperemic flow with increased risk of adverse clinical outcomes suggests that micro-vascular function may be an important prognostic marker in patients with HF.
[EX A]: Is reactive hyperemia associated with adverse clinical outcomes in heart failure?

[EX Q]: Context: The membrane protein CD46, a ubiquitous cell surface pathogen receptor, can bind Streptococcus to trigger cell autophagy, which is a critical step in the control of infection.', 'In this study, we found a new splice variant designated CD46 transcript variant (CD46-TV). The splice variant is characterized by the retention of a 48\xa0bp sequence from intron 8 of the bovine CD46 gene, which encodes a putative protein enlarged by 16 amino acids. CD46-TV mRNA was found to be over expressed in mastitis-infected mammary gland tissues relative to healthy tissues. A single nucleotide polymorphism (c. 1033\u2009+\u20092184 C\u2009>\u2009T) in the exonic splicing enhancer (ESE) motif region was shown to result in the CD46-TV aberrant splice variant through constructing alternative alleles using the pSPL3 exon capturing vector and transfecting these into 293\xa0T cells. Allelic frequency in 56,682 individuals belonging to 112 Bos taurus, Bos indicus, Bos javanicus, Bos grunniens and Bos mutus, etc. suggests that the C allele (80.09%) is the ancestral allele. Association analysis found that the mean genomic estimated breeding values (gEBV) for milk somatic cell score and the occurrence of clinical mastitis, as well as the milk somatic cell score of Chinese Holsteins with the CT genotype was lower than those of individuals with either the CC or TT genotypes. The mean gEBV for udder health synthesis for the TT genotype was greater than those for the CC or CT genotypes.
Answer: Our findings suggest that the CD46 gene likely plays a critical role in the risk of mastitis caused by Streptococcus in dairy cows via an alternative splicing mechanism caused by a functional mutation in intron 8. Our data also underline the importance of variation within ESEs in regulating transcript processing.
[EX A]:
Does a SNP in intron 8 of CD46 cause a novel transcript associated with mastitis in Holsteins?