Tissue gene expression profiles and communication networks inform candidate blood biomarker identification in psoriasis and atopic dermatitis.

Overlapping clinical and pathomechanistic features can complicate the diagnosis and treatment of inflammatory skin diseases, including psoriasis and atopic dermatitis (AD). Spatial transcriptomics allows the identification of disease- and cell-specific molecular signatures that may advance biomarker development and future treatments. This study identified transcriptional signatures in keratinocytes and sub-basal CD4+ and CD8+ T lymphocytes from patients with psoriasis and AD. In silico prediction of ligand:receptor interactions delivered key signalling pathways (interferon, effector T cells, stroma cell and matrix biology, neuronal development, etc.). Targeted validation of selected transcripts, including CCL22, RELB, and JUND, in peripheral blood T cells suggests the chosen approach as a promising tool also in other inflammatory diseases. Psoriasis and AD are characterized by transcriptional dysregulation in T cells and keratinocytes that may be targeted therapeutically. Spatial transcriptomics is a valuable tool in the search for molecular signatures that can be used as biomarkers and/or therapeutic targets.

Daily Assessment of Stressful events and Coping in early post-operative recovery after colorectal cancer surgery.

This study describes the most stressful events and coping strategies used by patients with colorectal cancer 4-6 weeks after surgery and whether the coping strategies were considered helpful or not. For the investigation of situational coping, an exploratory design was used. One hundred and five patients from three Swedish hospitals were included to fill in the Daily Coping Assessment. Most stressful event, number and types of pre-defined coping strategies used, and if the coping strategy used was considered helpful or not, were measured for 5 days. Of 523 diary entries, 180 reported no stressful events. The most stressful event, also with worst level of control and expectation, was "Pain," followed by "Nausea/vomiting." The areas causing most stressful events were "Bowel-related" and "Surgery and treatment-related problems." Acceptance and Direct action were the most frequently used coping strategies. There was a wide range of perceived helpfulness if coping strategies were placed in relation to specific areas of events. The conclusion was that patients revealed several strategies for coping with stressful events but needed a higher level of preparedness for what might come and therefore need to be given appropriate support to cope during the early recovery phase. Such support is suggested to be person-centred and oriented towards individually adapting standardised regimens, given the variety of situations to which the stressful events reported in the study were related.

Development and validation of the preparedness for Colorectal Cancer Surgery Questionnaire: PCSQ-pre 24.

PURPOSE: The aims of the study were to develop and psychometrically evaluate a patient-reported outcome instrument for the measurement of preoperative preparedness in patients undergoing surgery for colorectal cancer. METHODS: This study was conducted in two stages: a) instrument development (item generation, construction of items and domains), empirical verification and b) instrument evaluation. A questionnaire with 28 items measuring preparedness for surgery was developed covering four domains and was tested for content validity with an expert panel and with patients. Psychometric testing of the questionnaire was conducted on 240 patients undergoing elective surgery for colorectal cancer. RESULTS: The scale content validity index of the preparedness items was 0.97. The final version consisted of 24 items measuring 4 subscales: Searching for and making use of information, Understanding and involvement in the care process, Making sense of the recovery process and Support and access to medical care. Confirmatory factor analysis revealed good model fit with standardized factor loadings ranging from 0.58 to 0.97. A well-fitting second-order factor model provided support for a total preparedness score with second-order factor loadings ranging from 0.75 to 0.93. The ordinal alpha values of the four latent factors ranged from 0.92 to 0.96, indicating good internal consistency. The polyserial correlations with the total score were 0.64 (p < 0.01) for the overall preparedness question and 0.37 (p < 0.01) for overall well-being. CONCLUSION: The Swedish Preparedness for Colorectal Cancer Surgery Questionnaire for use in the preoperative phase demonstrated good psychometric properties based on a sound conceptualization of preparedness.

Staphylococcus aureus colonization related to severity of hand eczema.

Knowledge on Staphylococcus aureus colonization rates and epidemiology in hand eczema is limited. The aim of this study was to clarify some of these issues. Samples were collected by the "glove juice" method from the hands of 59 patients with chronic hand eczema and 24 healthy individuals. Swab samples were taken from anterior nares and throat from 43 of the 59 patients and all healthy individuals. S. aureus were spa typed and analysed by DNA-microarray-based genotyping. The extent of the eczema was evaluated by the hand eczema extent score (HEES). The colonization rate was higher on the hands of hand eczema patients (69 %) compared to healthy individuals (21 %, p < 0.001). This was also seen for bacterial density (p = 0.002). Patients with severe hand eczema (HEES ≥ 13) had a significantly higher S. aureus density on their hands compared to those with milder eczema (HEES = 1 to 12, p = 0.004). There was no difference between patients and healthy individuals regarding colonization rates in anterior nares or throat. spa typing and DNA-microarray-based genotyping indicated certain types more prone to colonize eczematous skin. Simultaneous colonization, in one individual, with S. aureus of different types, was identified in 60-85 % of the study subjects. The colonization rate and density indicate a need for effective treatment of eczema and may have an impact on infection control in healthcare.

'Just so you know, the patient is staff': healthcare professionals' perceptions of caring for healthcare professional-patients.

OBJECTIVE: To explore healthcare professionals' conceptions of the care of patients who are also healthcare professionals. DESIGN: Explorative, with a qualitative, phenomenographic approach. PARTICIPANTS AND SETTING: 16 healthcare personnel within different professions (doctors, nurses, assistant nurses, physiotherapists, occupational therapists) were interviewed about the care of 32 patients who were themselves members of different healthcare professions, in one healthcare organisation in Sweden. RESULTS: The care of patients who are healthcare professionals was conceived in five different ways, as: usual, dutiful, prioritised and secure, insecure and responsive. An initial conception was that their care was usual, just as for any other patient, and also a perceived duty to treat them and to protect their right to be a patient--as any other patient. Exploring further, informants described that these patients did receive secure and prioritised care, as the informants experienced making a greater commitment, especially doctors giving privileges to doctor-patients. A conception of insecure care infused the informants' descriptions. This comprised of them feeling intimidated in their professional role, feeling affected by colleagues' stressful behaviour and ambiguity whether the healthcare professional-patient could be regarded as a competent professional. The deepest way of understanding care seemed to be responsive care, such as acknowledging and respecting the patient's identity and responding to their wishes of how treatment was to be met. CONCLUSIONS: Caring for healthcare professionals seems to trigger different ethical approaches, such as deontology and ethics of care. According to ethics of care, the findings may indeed suggest that these patients should be cared for just as any other patients would be, but only if this means that they are cared for as persons, that is, they are given 'person-centred care'. This would imply balancing between acknowledging the vulnerable patient in the colleague and acknowledging the identity of the colleague in the patient.

High physical activity in young children suggests positive effects by altering autoantigen-induced immune activity.

Physical activity in children is associated with several positive health outcomes such as decreased cardiovascular risk factors, improved lung function, enhanced motor skill development, healthier body composition, and also improved defense against inflammatory diseases. We examined how high physical activity vs a sedentary lifestyle in young children influences the immune response with focus on autoimmunity. Peripheral blood mononuclear cells, collected from 55 5-year-old children with either high physical activity (n = 14), average physical activity (n = 27), or low physical activity (n = 14), from the All Babies In Southeast Sweden (ABIS) cohort, were stimulated with antigens (tetanus toxoid and beta-lactoglobulin) and autoantigens (GAD65 , insulin, HSP60, and IA-2). Immune markers (cytokines and chemokines), C-peptide and proinsulin were analyzed. Children with high physical activity showed decreased immune activity toward the autoantigens GAD65 (IL-5, P < 0.05), HSP60 and IA-2 (IL-10, P < 0.05) and also low spontaneous pro-inflammatory immune activity (IL-6, IL-13, IFN-γ, TNF-α, and CCL2 (P < 0.05)) compared with children with an average or low physical activity. High physical activity in young children seems to have positive effects on the immune system by altering autoantigen-induced immune activity.

Structure and content in consultations with patients undergoing surgery for colorectal cancer.

PURPOSE: To explore the structure and content of pre-planned consultations as part of the care and treatment of patients undergoing surgery for colorectal cancer. METHODS: The study was based on 50 transcripts of audio-recorded pre-planned consultations between seven patients and 36 healthcare professionals from the time of diagnosis, pre-operative consultation, discharge consultation and pathology report in a colorectal unit. RESULTS: The spread of consultation time between professions was considerable. Total mean consultation time for patients during the care process (7 consultations/patient) was 111 min (range 83-191). The mean consultation time for surgeons was 18 min (7-40), anaesthesiologists 12 min (5-18) and nurses 14 min (5-49). Patients took up 40% of the word space, healthcare professionals used 59% and significant others 1%. Word space changed in such a way that the patient became more active towards the final consultation. Neither during the diagnosis consultation nor during the pre-operative consultation did the patients meet the operating surgeon. Six major subjects emerged: general health, diagnosis, surgical procedure, pre-operative preparations, recovery and treatment and follow-up. CONCLUSIONS: There is a need for clearer structure in the consultations. Most consultations lacked a clear introduction to the subject of the conversation. The study makes it possible to develop methods and structure for supporting conversations in which the patient is given space to help with the difficult issues present after undergoing surgery for colorectal cancer. The study also contributes to providing knowledge of how to organise surgical consultations in order to optimise person-centeredness, teamwork and clinical efficiency.

Potential role of a navigator gene NAV3 in colorectal cancer.

BACKGROUND: The recently described navigator proteins have a multifaceted role in cytoskeletal dynamics. We report here on the relevance of one of them, navigator 3 (NAV3), in colorectal cancer (CRC). METHODS: We analysed changes in chromosome 12 and NAV3 copy number in CRC/adenoma samples of 59 patients and in 6 CRC cell lines, using fluorescence in situ hybridisation, loss of heterozygosity, and array-CGH. NAV3 target genes were identified by siRNA depletion, expression arrays, and immunohistochemistry. RESULTS: NAV3 deletion and chromosome 12 polysomy were detected in 30 and 70% of microsatellite stability (MSS) carcinomas, in 23 and 30% of adenomas and in four of six CRC cell lines. NAV3 amplification was found in 25% of MSS samples. NAV3 alterations correlated with lymph node metastasis. In normal colon cells, NAV3 silencing induced upregulation of interleukin 23 receptor (IL23R) and gonadotropin releasing hormone receptor. In MSS and microsatellite instability tumours, IL23R immunoreactivity correlated with Dukes' staging and lymph node metastases, whereas nuclear beta-catenin correlated with lymph node metastases only. CONCLUSION: NAV3 copy number changes are frequent in CRC and in adenomas, and upregulation of IL23R, following NAV3 silencing, strongly correlates with Dukes' staging and lymph node metastases. This suggests that NAV3 has a role in linking tissue inflammation to cancer development in the colon.

Stoma-related complications and stoma size - a 2-year follow up.

AIM: The purpose of the study was to prospectively describe stoma configuration and evaluate stoma-related complications and their association with possible risk factors. METHOD: All elective patients (n = 180) operated on with a formation of colostomy, ileostomy or loop-ileostomy between 2003 and 2005 were included in the study. Follow up took place on the ward postoperatively and five times during 2 years after discharge. On these occasions the diameter and height of the stoma were recorded. Complications such as peristomal skin problems, necrosis, leakage caused by a low stoma, stenosis, granuloma formation, prolapse and peristomal hernia formation were evaluated. RESULTS: Most complications occurred 2 weeks after discharge; 53% of patients with colostomies, 79% with loop-ileostomies and 70% of patients with end-ileostomy had one or more complications. The most common complication was skin problems and it was most common in patients with end-ileostomies (60%) and loop-ileostomies (73%). Postoperatively at ward review, the most common complication was necrosis, which occurred in 20% of patients with a colostomy. Granuloma formation was most frequent in colostomies. Almost all patients with an end-ileostomy and loop-ileostomy with a height lower than 20 mm had leakage and skin problems as had half of the patients with a colostomy height lower than 5 mm. CONCLUSION: To prevent stoma-related complications, it is important to produce an adequate height of the stoma, with early and regular follow ups and adjustment of the appliance. To work closely in collaboration with the colorectal surgeons is of utmost important to provide feedback and in turn, to improve stoma outcome.

Temporal trends of HLA genotype frequencies of type 1 diabetes patients in Sweden from 1986 to 2005 suggest altered risk.

The aim of this study was to compare the frequency of human leukocyte antigen (HLA) genotypes in 1-18-year-old patients with type 1 diabetes newly diagnosed in 1986-1987 (n = 430), 1996-2000 (n = 342) and in 2003-2005 (n = 171). We tested the hypothesis that the HLA DQ genotype distribution changes over time. Swedish type 1 diabetes patients and controls were typed for HLA using polymerase chain reaction amplification and allele specific probes for DQ A1* and B1* alleles. The most common type 1 diabetes HLA DQA1*-B1*genotype 0501-0201/0301-0302 was 36% (153/430) in 1986-1987 and 37% (127/342) in 1996-2000, but decreased to 19% (33/171) in 2003-2005 (P \ 0.0001). The 0501-0201/0501-0201 genotype increased from 1% in 1986-1987 to 7% in 1996-2000 (P = 0.0047) and to 5% in 2003-2005 (P > 0.05). This study in 1-18-year-old Swedish type 1 diabetes patients supports the notion that there is a temporal change in HLA risk.

IA-2 autoantibodies in incident type I diabetes patients are associated with a polyadenylation signal polymorphism in GIMAP5.

In a large case-control study of Swedish incident type I diabetes patients and controls, 0-34 years of age, we tested the hypothesis that the GIMAP5 gene, a key genetic factor for lymphopenia in spontaneous BioBreeding rat diabetes, is associated with type I diabetes; with islet autoantibodies in incident type I diabetes patients or with age at clinical onset in incident type I diabetes patients. Initial scans of allelic association were followed by more detailed logistic regression modeling that adjusted for known type I diabetes risk factors and potential confounding variables. The single nucleotide polymorphism (SNP) rs6598, located in a polyadenylation signal of GIMAP5, was associated with the presence of significant levels of IA-2 autoantibodies in the type I diabetes patients. Patients with the minor allele A of rs6598 had an increased prevalence of IA-2 autoantibody levels compared to patients without the minor allele (OR=2.2; Bonferroni-corrected P=0.003), after adjusting for age at clinical onset (P=8.0 x 10(-13)) and the numbers of HLA-DQ A1*0501-B1*0201 haplotypes (P=2.4 x 10(-5)) and DQ A1*0301-B1*0302 haplotypes (P=0.002). GIMAP5 polymorphism was not associated with type I diabetes or with GAD65 or insulin autoantibodies, ICA, or age at clinical onset in patients. These data suggest that the GIMAP5 gene is associated with islet autoimmunity in type I diabetes and add to recent findings implicating the same SNP in another autoimmune disease.

SUMO4 M55V polymorphism affects susceptibility to type I diabetes in HLA DR3- and DR4-positive Swedish patients.

SUMO4 M55V, located in IDDM5, has been a focus for debate because of its association to type I diabetes (TIDM) in Asians but not in Caucasians. The current study aims to test the significance of M55V association to TIDM in a large cohort of Swedish Caucasians, and to test whether M55V is associated in those carrying human leukocyte antigen (HLA) class II molecules. A total of 673 TIDM patients and 535 age- and sex-matched healthy controls were included in the study. PCR-RFLP was performed to identify the genotype and allele variations. Our data suggest that SUMO4 M55V is not associated with susceptibility to TIDM by itself. When we stratified our patients and controls based on heterozygosity for HLA-DR3/DR4 and SUMO4 genotypes, we found that presence of SUMO4 GG increased further the relative risk conferred by HLA-DR3/DR4 to TIDM, whereas SUMO4 AA decreased the risk. From the current study, we conclude that SUMO4 M55V is associated with TIDM in association with high-risk HLA-DR3 and DR4, but not by itself.

Peste des petits ruminants (PPR) outbreak in Tajikistan.

The occurrence of outbreaks of peste des petits ruminants (PPR) in three districts of Tajikistan is described. The causal strain (PPR Tajikistan) was characterized and the sequence of its N gene was compared with that of 43 other strains isolated since 1968 in Africa, the Middle East and Asia. The study demonstrated (1) the value of the N gene as a target in comparing isolates obtained over an extended period of evolution, and (2) that clustering was related to the geographical origin of strains.

The hormone-sensitive lipase C-60G promoter polymorphism is associated with increased waist circumference in normal-weight subjects.

OBJECTIVE: Hormone-sensitive lipase (HSL) is a key enzyme in the mobilization of fatty acids from triglyceride stores in adipocytes. The aim of the present study was to investigate the role of the HSL gene promoter variant C-60G, a polymorphism which previously has been associated with reduced promoter activity in vitro, in obesity and type 2 diabetes. DESIGN: We genotyped two materials consisting of obese subjects and non-obese controls, one material with offspring-parents trios, where the offspring was abdominally obese and one material with trios, where the offspring had type 2 diabetes or impaired glucose homeostasis. HSL promoter containing the HSL C-60G G-allele was generated and tested against a construct with the C-allele in HeLa cells and primary rat adipocytes. HSL mRNA levels were quantified in subcutaneous and visceral fat from 33 obese subjects. RESULTS: We found that the common C-allele was associated with increased waist circumference and WHR in lean controls, but there was no difference in genotype frequency between obese and non-obese subjects. There was a significant increased transmission of C-alleles to the abdominally obese offspring but no increased transmission of C-alleles was observed to offspring with impaired glucose homeostasis. The G-allele showed reduced transcription in HeLa cells and primary rat adipocytes. HSL mRNA levels were significantly higher in subcutaneous compared to visceral fat from obese subjects. CONCLUSION: The HSL C-60G polymorphism is associated with increased waist circumference in non-obese subjects.

A polymorphism in the adiponectin gene influences adiponectin expression levels in visceral fat in obese subjects.

OBJECTIVE: Reduced serum adiponectin levels have been found in obesity and type 2 diabetes and variations in the adiponectin gene (APM1) have been associated with type 2 diabetes and features of the metabolic syndrome in different populations. STUDY DESIGN: Here, we investigated the expression of APM1 in adipose tissue and studied the relationship between variation in APM1 expression, the APM1 G276T polymorphism, the common PPARG Pro12Ala polymorphism and clinical features of 36 morbidly obese (body mass index (BMI) 41.5 +/- 4.9 kg/m2) nondiabetic subjects. RESULTS: APM1 mRNA expression in visceral fat was correlated with serum adiponectin levels (r = 0.54, P = 0.012). In visceral, but not in subcutaneous, adipose tissue APM1 mRNA level was 38% higher among carriers of the APM1 G276T T allele (G/T and T/T) than among carriers of the G/G genotype (0.91 +/- 0.06 for G/T and T/T carriers vs 0.66 +/- 0.09 for G/G carriers, P = 0.013). Carriers of the T allele also had significantly higher body fat percent compared to G/G carriers (65 +/- 6 vs 56 +/- 10%, P = 0.011). CONCLUSION: Our results indicate that genetic variation in APM1 influences the expression of the gene in visceral adipose tissue and suggest a potential role for such variation in regulation of body fat accumulation in obese subjects.

Abnormal crossing of the optic fibres shown by evoked magnetic fields in patients with ocular albinism with a novel mutation in the OA1 gene.

AIM: To perform genealogical and clinical studies in Finnish families with X linked ocular albinism (OA1), including characterisation of the potential misrouting of optic fibres by evaluating visual evoked magnetic fields (VEFs), and to determine the mutation behind the disease. METHODS: Three families with OA1 were clinically examined. VEFs were measured in two affected males and in one female carrier to characterise the cortical activation pattern after monocular visual stimulation. The neuronal sources of the VEFs were modelled with equivalent current dipoles (ECDs) in a spherical head model. All coding exons of the OA1 gene were screened for mutations by single strand conformation analysis and direct polymerase chain reaction sequencing. RESULTS: Genealogical studies revealed that the three families were all related. The affected males had foveal hypoplasia with reduced visual acuity varying from 20/200 to 20/50, variable nystagmus, iris transillumination, and hypopigmentation of the retinal pigment epithelium. The ECD locations corresponding to the VEFs revealed abnormal crossing of the optic fibres in both affected males, but not in the carrier female. A novel point mutation, leading to a STOP codon, was identified in the fifth exon of the OA1 gene. CONCLUSIONS: The data indicate that the novel mutation 640C>T in the OA1 gene is the primary cause of the eye disease in the family studied. VEFs with ECD analysis was successfully used to demonstrate abnormal crossing of the optic fibres.

Role of the FOXC2 -512C>T polymorphism in type 2 diabetes: possible association with the dysmetabolic syndrome.

OBJECTIVE: Overexpression of the human transcription factor FOXC2 gene (FOXC2) protects against insulin resistance in mice and a common FOXC2 polymorphism (-512C>T) has been suggested to be associated with insulin resistance in humans. Here, we addressed the potential role for FOXC2 as a candidate gene for type 2 diabetes and associated phenotypes. MATERIALS AND METHODS: A case-control study was performed in 390 type 2 diabetic patients and 307 control subjects. The number of patients was increased to a total of 768 subjects for further study of phenotypic differences relating to the dysmetabolic syndrome relative to genetic variation. The FOXC2 -512C>T polymorphism was genotyped by a restriction fragment length polymorphism PCR assay. RESULTS: FOXC2 -512C>T allele and genotype distribution did not differ between patients with type 2 diabetes and control subjects, but the C/C genotype was associated with increased body mass index (BMI, kg/m2) (Pa=0.03) among type 2 diabetic patients. The FOXC2 -512C>T polymorphism was a significant independent predictor of BMI (P=0.001) in a multiple regression model including age, gender and affection status. We found no significant association with type 2 diabetes-related metabolic parameters but that the C-allele (P=0.01) and C/C and C/T genotypes (P=0.03) were significantly over-represented in type 2 diabetic males with a concomitant diagnosis of dysmetabolic syndrome. CONCLUSION: We conclude that FOXC2 is associated with obesity and metabolic deterioration but does not contribute to an increased risk for type 2 diabetes.

Body composition in patients with short bowel syndrome: an assessment by bioelectric impedance spectroscopy (BIS) and dual-energy absorptiometry (DXA).

OBJECTIVE: To describe body composition in patients with short bowel syndrome (SBS) by using bioelectric impedance spectroscopy (BIS), dual-energy X-ray absorptiometry (DXA) measurements and anthropometrical-derived estimates. SUBJECTS: In all, 19 patients were included, mean age 54 y, range 36-77 (F/M=11/8). Mean BMI was 21.5 kg/m(2). Eight patients were on home parenteral nutrition (HPN). METHODS: Total body water (TBW), intracellular water and extracellular water were assessed by BIS. TBW were derived from DXA. Fat-free mass (FFM) was assessed by BIS and DXA. TBW and FFM were predicted according to an empirical formula. Differences were analysed using the Bland-Altman method. RESULTS: The mean difference between TBW (DXA) and TBW (BIS) was -1.1 l in women and -1.8 l in men. For FFM, the mean difference between FFM (DXA) and FFM (BIS) was -1.7 kg in women and -2.5 kg in men. The mean difference between TBW (DXA) and TBW (BIS) for all patients was -1.2 l and limits of agreement were (-7.80-5.40). Hydration of FFM assessed by BIS gave a mean of 0.75 (0.08). CONCLUSION: The limits of agreement (Bland-Altman) between DXA and BIS were wide, indicating that methods are not interchangeable, which limits its clinical utility. Most of our patients with SBS were maintained in a stable clinical condition within normal limits of body weight and BMI. FFM and TBW did not appear to be altered in ileostomates or those on HPN.

What concerns subjects with inflammatory bowel disease and an ileostomy?

BACKGROUND: The greatest concern of patients with inflammatory bowel disease (IBD) is of having an ileostomy. The aim of this study was to describe worries and concerns in subjects with IBD and an ileostomy, and aspects of quality of life and coping strategies. METHODS: 21 subjects with an ileostomy were included, mean age 51, range 36-65 (F/M = 12/9), Crohn disease (CD) n = 14, ulcerative colitis (UC) n = 6 and indeterminate colitis (IDC) n = 1. Worries and concerns were assessed using the rating form of IBD patient concerns (RFIPC). Health-related quality of life (HRQOL) was assessed using Short Form 36 (SF-36) and compared with a matched group for age and gender from the general population. Subjects' definition of quality of life, as well as perceived quality of life on a visual analogue scale, was evaluated. Coping strategies were investigated using the Jalowiec coping scale (JCS 40). RESULTS: Greatest concerns were related to intimacy, access to quality medical care, energy level, loss of sexual drive, producing unpleasant odours, being a burden, ability to perform sexually, attractiveness and feelings about the body. Vitality was significantly reduced compared to controls. Subjects' definition of good quality of life mainly concerned social dimensions of life and health. Low values on perceived quality of life indicated greater concerns. Confrontational coping style was most frequently used. CONCLUSION: The greatest concern for subjects with an ileostomy was intimacy. Vitality was reduced compared to controls. Integrating items of concern into counselling may result in greater coping ability and improved quality of life.

Pro-opiomelanocortin gene is associated with serum leptin levels in lean but not in obese individuals.

OBJECTIVE: Mutations in the pro-opiomelanocortin and melanocortin 4 receptor genes (POMC and MC4R) cause monogenic obesity, and the POMC locus (2p21) has been linked to leptin levels and body mass index (BMI). We searched for monogenic obesity due to mutations in POMC and MC4R among morbidly obese Swedes and studied the association of POMC variants with BMI and serum leptin levels. DESIGN: MC4R and POMC were screened for mutations in 102 obese Swedish subjects (40+/-11 y, 41.3+/-5.0 kg/m(2)) using the single-strand conformation polymorphism technique. The detected polymorphisms were genotyped in 118 lean control subjects (56+/-11 y, 22.6+/-1.3 kg/m(2)) and studied for association with BMI and serum leptin levels. RESULTS: No cases of monogenic obesity due to mutations in POMC or MC4R were identified and none of the four common POMC polymorphisms (RsaI, ins56, Glu188Gly and C8246T) were associated with obesity. Lean carriers of the C8246T CC-genotype had higher serum leptin levels compared to CT or TT carriers (9.7+/-6.6 vs 6.7+/-4.4 microg/l, P=0.003 for leptin levels adjusted for age, sex and BMI in regression analysis), especially lean females (P=0.004) and lean female carriers with the C8246T(CC)/RsaI(--or +-) genotype combinations (P<0.0005). Neither the C8246T CC-genotype nor the C8246T(CC)/RsaI(--or +-) were associated with serum leptin levels in obese subjects. CONCLUSIONS: Monogenic forms of obesity due to mutations in POMC and MC4R are rare in Swedish obese patients. Polymorphisms in POMC are associated with variation in serum leptin levels within the normal range in healthy lean but not in obese individuals.