The impact of the Catechol-O-methyltransferase Val158Met polymorphism on survival in the general population – the HUNT study

Background  

The catechol-O-methyltransferase (COMT) gene contains a functional polymorphism, Val158Met which has been related to common diseases like cancer, psychiatric illness and myocardial infarction. Whether the Val158Met polymorphism is associated with survival has not been evaluated in the general population. The aim of this prospective study was to evaluate the impact of codon 158 COMT gene polymorphism on survival in a population-based cohort.     

Time dynamics of autoantibodies are coupled to phenotypes and add to the heterogeneity of autoimmune diabetes in adults: the HUNT study,Norway

Aims  

The aetiology of latent autoimmune diabetes in adults (LADA), assessed by autoimmune markers, is insufficiently clarified. We cross-sectionally investigated the prevalence and prospectively the prediabetic and postdiabetic presence of antibodies to glutamic acid decarboxylase (GADA), insulinoma-associated protein 2 and zinc transporter 8 in LADA and in type 1 diabetes.     

Associations of serum 25-hydroxyvitamin D level with incidence of lung cancer and histologic types in Norwegian adults: a case-cohort analysis of the HUNT study

Previous prospective studies have shown inconsistent associations between serum 25-hydroxyvitamin D [25(OH)D] level and lung cancer incidence. The aim of the present study was to explore the associations of serum 25(OH)D levels with incidence of lung cancer overall and different histologic types. We performed a population-based prospective case-cohort study including 696 incident lung cancer cases and 5804 individuals in a subcohort who participated in the second survey of the Nord-Trøndelag Health Study in Norway. Cox proportional hazards regression models counting for the case-cohort design were used to estimate hazard ratios (HRs) with 95% confidence interval (CIs) for lung cancer overall or histologic types in relation to serum 25(OH)D levels. Compared with the fourth season-specific quartile of 25(OH)D (median 68.0 nmol/L), lower 25(OH)D levels were not associated with the incidence of overall, small or squamous cell lung cancer. However, the risk of adenocarcinoma was lower in the second and third quartiles (median 39.9 and 51.5 nmol/L) compared with the fourth quartile, with HRs of 0.63 (95% CI 0.41–0.98) and 0.58 (0.38–0.88), respectively. The associations of lower levels of 25(OH)D with a reduced risk of adenocarcinoma were only observed in the overweight/obese subjects [HRs for second and third quartiles: 0.40 (0.22–0.72) and 0.50 (0.27–0.92)] but not in the normal weight subjects [HRs: 0.95 (0.52–1.75) and 0.60 (0.32–1.10)]. Serum 25(OH)D levels were not associated with the risk of lung cancer in general. The observation that lower 25(OH)D levels were associated with a lower risk of adenocarcinoma should be interpreted with caution.     

Morphine glucuronide-to-morphine plasma ratios are unaffected by the UGT2B7 H268Y and UGT1A1*28 polymorphisms in cancer patients on chronic morphine therapy

OBJECTIVE: UDP-glucuronosyltransferase (UGT) 2B7 is the major UGT isoform responsible for the 3- and 6-glucuronidation of morphine in humans. Studies in rats have indicated that UGT1A1 may also contribute to the formation of morphine 3-glucuronide (M3G). Our objective was to investigate whether the UGT2B7 H268Y and UGT1A1*28 polymorphisms contribute to the variability in morphine glucuronide-to-morphine plasma ratios among cancer patients undergoing analgesic therapy with morphine. METHODS: Seventy patients with normal hepatic and renal function using slow-release morphine to relieve cancer pain were included. UGT2B7 genotyping was performed using restriction enzyme analysis of polymerase chain reaction (PCR)-amplified DNA fragments. Wild-type and variant alleles of the UGT1A1 gene were identified using sizing of PCR-amplified fragments. Morphine 6-glucuronide (M6G)/morphine, M3G/morphine, and M3G/M6G plasma ratios were compared between genotypes. RESULTS: The M3G/morphine, M6G/morphine, and M3G/M6G plasma ratios varied 16-, 42-, and sevenfold, respectively, among individuals. No statistically significant differences in plasma ratios were found between individuals possessing UGT2B7 H/H ( n=20), H/Y ( n=30), or Y/Y ( n=20) genotypes. Five patients were homozygous for the UGT1A1 TA(7) allele, which is associated with reduced UGT1A1 gene expression. However, the mean M3G/M6G and M3G/morphine plasma ratios in TA(7) homozygous subjects did not differ significantly from those of heterozygous or homozygous wild-type (TA(6)) individuals. CONCLUSION: The UGT2B7 H268Y polymorphism cannot account for the considerable variation in glucuronide-to-morphine ratios in cancer patients. Moreover, the contribution of UGT1A1 to the formation of M3G appears to be of minor biological significance, at least in a UGT2B7 background.     

Variable response to opioid treatment: any genetic predictors within sight?

The aim of this literature review is to summarize and discuss the available evidence for a relationship between polymorphisms in human genes and variability in opioid analgesia and side effects among patients treated for moderate or severe pain. The evidence supporting a role of certain alleles, genotypes or haplotypes in modulation of opioid analgesia is derived from a limited number of studies, a limited number of genes and a limited number of opioids. Although several interesting candidates have emerged as potentially relevant factors, only for one polymorphism, the prevalent 118A>G of the micro-opioid receptor, the accumulated evidence is sufficient to suggest a clinically relevant effect for an opioid used for moderate or severe pain. Still the data are valid only at the group level and cannot be used to predict treatment outcome in individual patients. Only a few of the symptoms often seen as opioid adverse effects in palliative care, such as nausea, vomiting, constipation and sedation, have been associated with genetic variants in various genes, but the results have been based on case reports, healthy volunteers or post-operative patients. So far, there is no clear evidence that genetic markers can be used to predict opioid efficacy or adverse effects in palliative care patients. This reflects the general lack of studies performed in the context of palliative care, the lack of sufficiently scaled studies and the lack of international standards for the assessment of subjective symptoms.     

Doing participant observation in a psychiatric hospital-- research ethics resumed

Social scientists who employ participant observation methods in medical settings are often held accountable for their research methods, specifically in regard to medical research ethics. However, the medical research ethics tradition rubs uneasily against participant observation and the anthropological understanding of the research process. The underlying premise for considering research ethics in the current case is the notion of the vulnerability of psychiatric patients as a participant group. Based on this notion of vulnerability among psychiatric patients, this article discusses the epistemological grounds for vulnerability in anthropological and medical research ethics. The authors draw on their experience with the Regional Committee for Medical Research Ethics in Norway, and the consequences of the guidelines used for participant observation as a research method in a psychiatric hospital. Social science researchers are required to follow medical ethical guidelines, such as informed consent, the principle of voluntariness, and estimation of risks and benefits. Ethnographers have found these guidelines to be obstructive when doing social science research in a psychiatric hospital. The article suggests the need for reformulation of research guidelines for participant observation in medical settings.     

What did the doctor say--what did the patient hear? Operational knowledge in clinical communication

OBJECTIVES: We aim to introduce Piaget's concept of 'operational knowledge' from the cognitive theory of learning--as a contribution to the broader understanding of clinical interaction. METHOD: Our study involves a theoretical presentation of different kinds and levels of human understanding, illustrated by a case story in which the difference between operational and figurative knowledge was demonstrated. This study used the case story of a male patient aged 80, who was suffering from ulcerative colitis. We appealed to the reader's perceived relevance of these perspectives, in order to understand what was going on between doctor and patient. RESULTS: The case story demonstrates the phenomenon of operational knowledge in the patient, the close links between communicative action and cognitive understanding, and the importance for the doctor of reflecting upon this level of interaction. CONCLUSION: According to the patient-centred clinical method, the doctor should explore the social and emotional context of the patient in order to understand the meaning of the illness. We suggest that a cognitive dimension should also be added, and that the concept of 'operational knowledge' might be useful for such investigations.      

The association between headache and Val158Met polymorphism in the catechol–O–methyltransferase gene: the HUNT Study

The catechol–O–methyltransferase (COMT) gene contains a functional polymorphism, Val158Met, that has been found to influence human pain perception, and one study has found that migraine was less likely among those with the Val/Val polymorphism. In the 1995–97 Nord–Trøndelag Health (HUNT) Study, the association between the Val158Met polymorphism and headache was evaluated in a random sample of 2451 individuals. No association between Val158Met polymorphism and migraine was found. Among women, a lower prevalence of non–migrainous headache was found among individuals with the Val/Val genotype than among those with other genotypes (26.2% vs. 33.6%, p=0.04). That non–migrainous headache was less likely among women with the Val/Val genotype may be an incidental finding, but should be investigated in further studies.