Expansion of the human μ-opioid receptor gene architecture: novel functional variants

The μ-opioid receptor (OPRM1) is the principal receptor target for both endogenous and exogenous opioid analgesics. There are substantial individual differences in human responses to painful stimuli and to opiate drugs that are attributed to genetic variations in OPRM1. In searching for new functional variants, we employed comparative genome analysis and obtained evidence for the existence of an expanded human OPRM1 gene locus with new promoters, alternative exons and regulatory elements. Examination of polymorphisms within the human OPRM1 gene locus identified strong association between single nucleotide polymorphism (SNP) rs563649 and individual variations in pain perception. SNP rs563649 is located within a structurally conserved internal ribosome entry site (IRES) in the 5′-UTR of a novel exon 13-containing OPRM1 isoforms (MOR-1K) and affects both mRNA levels and translation efficiency of these variants. Furthermore, rs563649 exhibits very strong linkage disequilibrium throughout the entire OPRM1 gene locus and thus affects the functional contribution of the corresponding haplotype that includes other functional OPRM1 SNPs. Our results provide evidence for an essential role for MOR-1K isoforms in nociceptive signaling and suggest that genetic variations in alternative OPRM1 isoforms may contribute to individual differences in opiate responses

The effect of structured aerobic exercise on adherence, body mass index, hemoglobin A1c, and quality of life in type 1 and type 2 diabetes mellitus

Introduction Cardiovascular mortality risk is significantly increased by inactivity. Nevertheless, most patients with diabetes fail to achieve the recommended amount of weekly physical activity. Thus, strategies to establish and maintain an active lifestyle are required. Objective The aim of the present study was to examine the effects of a 6-month running program, Diabetes Programme Germany (DPD), on adherence, body mass index (BMI), hemoglobin A1c (HbA1c), and health-related quality of life (HRQOL). Methods/Results A retrospective analysis of 428 participants with type 1 (n = 177) and type 2 diabetes (n = 251) was performed. Adherence at 6 months was 75.5%. For participants who completed the program, there was a reduction in HbA1c of 0.3 +/- 1.0% (P = 7.5% (-1.4 +/- 1.7%, P <= .001). In a post-interventional survey (response rate: n = 83), participants reported an above-average physical HRQOL. Mental HRQOL showed no significant difference from other patients with diabetes. Conclusion The program's success was confirmed by a high adherence and significant reductions in BMI and HbA1c. Furthermore, a positive effect, especially on physical HRQOL, can be assumed

The increase in hemoglobin concentration with altitude varies among human populations

Decreased oxygen availability at high altitude requires physiological adjustments allowing for adequate tissue oxygenation. One such mechanism is a slow increase in the hemoglobin concentration ([Hb]) resulting in elevated [Hb] in high-altitude residents. Diagnosis of anemia at different altitudes requires reference values for [Hb]. Our aim was to establish such values based on published data of residents living at different altitudes by applying meta-analysis and multiple regressions. Results show that [Hb] is increased in all high-altitude residents. However, the magnitude of increase varies among the regions analyzed and among ethnic groups within a region. The highest increase was found in residents of the Andes (1 g/dL/1000 m), but this increment was smaller in all other regions of the world (0.6 g/dL/1000 m). While sufficient data exist for adult males and females showing that sex differences in [Hb] persist with altitude, data for infants, children, and pregnant women are incomplete preventing such analyses. Because WHO reference values were originally based on [Hb] of South American people, we conclude that individual reference values have to be defined for ethnic groups to reliably diagnose anemia and erythrocytosis in high-altitude residents. Future studies need to test their applicability for children of different ages and pregnant women