Objective. Fibromyalgia (FM) patients have signs of relentless sympathetic hyperactivity associated with hyporeactivity to stress. Adrenergic receptors (ARs) are parts of the sympathetic nervous system that are fundamental for maintenance of homeostasis. We undertook this study to correlate ␣-AR and ␤-AR gene polymorphisms with the presence of FM and with different domains of the FM syndrome as measured by the Fibromyalgia Impact Questionnaire (FIQ).Methods. We studied 78 Mexican FM patients and 48 age-matched controls as well as 78 Spanish FM patients and 71 controls. All subjects studied were women. Single-nucleotide polymorphisms (SNPs) of ␣ 1A -AR (rs574584, rs1383914, rs1048101, and rs573542), ␤ 2 -AR (rs1042713 and rs1042714), and ␤ 3 -AR (rs4994) were analyzed by 5 exonuclease TaqMan polymerase chain reaction. Polymorphic haplotypes were constructed after linkage disequilibrium analysis.Results. The ␤ 2 -AR AC haplotype was a risk factor for the presence of FM. This haplotype had an increased frequency in Mexican patients compared with Mexican controls (42.1% versus 30.5%; P ‫؍‬ 0.04). Similarly, 50.4% of Spanish patients had this haplotype compared with 40.0% of Spanish controls (P ‫؍‬ 0.05). In Spanish patients, the ␣ 1A -AR SNP rs1383914 was associated with the presence of FM (P ‫؍‬ 0.01), and the ␣ 1A -AR SNP rs1048101 was linked with FIQ disability (P ‫؍‬ 0.02). Mexican patients with the rs574584 GG genotype presented the highest FIQ score compared with Mexican patients with other genotypes (P ‫؍‬ 0.01), and in Mexicans SNP rs574584 was associated with FIQ morning stiffness (P ‫؍‬ 0.04) and with FIQ tiredness upon awakening (P ‫؍‬ 0.02).Conclusion. AR gene polymorphisms are related to the risk of developing FM and are also linked to different domains of the FM syndrome.

Background: A consistent line of investigation suggests that autonomic nervous system dysfunction may explain the multi-system features of fibromyalgia (FM); and that FM is a sympathetically maintained neuropathic pain syndrome. Dorsal root ganglia (DRG) are key sympathetic-nociceptive short-circuit sites. Sodium channels located in DRG (particularly Nav1.7) act as molecular gatekeepers for pain detection. Nav1.7 is encoded in gene SCN9A of chromosome 2q24.3 and is predominantly expressed in the DRG pain-sensing neurons and sympathetic ganglia neurons. Several SCN9A sodium channelopathies have been recognized as the cause of rare painful dysautonomic syndromes such as paroxysmal extreme pain disorder and primary erythromelalgia. The aim of this study was to search for an association between fibromyalgia and several SCN9A sodium channels gene polymorphisms. Methods: We studied 73 Mexican women suffering from FM and 48 age-matched women who considered themselves healthy. All participants filled out the Fibromyalgia Impact Questionnaire (FIQ). Genomic DNA from whole blood containing EDTA was extracted by standard techniques. The following SCN9A single-nucleotide polymorphisms (SNP) were determined by 5' exonuclease TaqMan assays: rs4371369; rs4387806; rs4453709; rs4597545; rs6746030; rs6754031; rs7607967; rs12620053; rs12994338; and rs13017637. Results: The frequency of the rs6754031 polymorphism was significantly different in both groups (P = 0.036) mostly due to an absence of the GG genotype in controls. Interestingly; patients with this rs6754031 GG genotype had higher FIQ scores (median = 80; percentile 25/75 = 69/88) than patients with the GT genotype (median = 63; percentile 25/75 = 58/73; P = 0.002) and the TT genotype (median = 71; percentile 25/75 = 64/77; P = 0.001). Conclusion: In this ethnic group; a disabling form of FM is associated to a particular SCN9A sodium channel gene variant. These preliminary results raise the possibility that some patients with severe FM may have a dorsal root ganglia sodium channelopathy.

No abstract

The catabolism and structure of high-density lipoproteins (HDL) may be the determining factor of their atheroprotective properties. To better understand the role of the kidney in HDL catabolism, here we characterized HDL subclasses and the catabolic rates of apo A-I in a rabbit model of proteinuria. Proteinuria was induced by intravenous administration of doxorubicin in New Zealand white rabbits (n = 10). HDL size and HDL subclass lipids were assessed by electrophoresis of the isolated lipoproteins. The catabolic rate of HDL-apo A-I was evaluated by exogenous radiolabelling with iodine-131. Doxorubicin induced significant proteinuria after 4 weeks (4.47 ± 0.55 vs. 0.30 ± 0.02 g/L of protein in urine, P < 0.001) associated with increased uremia, creatininemia, and cardiotoxicity. Large HDL2b augmented significantly during proteinuria, whereas small HDL3b and HDL3c decreased compared to basal conditions. HDL2b, HDL2a, and HDL3a subclasses were enriched with triacylglycerols in proteinuric animals as determined by the triacylglycerol-to-phospholipid ratio; the cholesterol content in HDL subclasses remained unchanged. The fractional catabolic rate (FCR) of [(131)I]-apo A-I in the proteinuric rabbits was faster (FCR = 0.036 h(-1)) compared to control rabbits group (FCR = 0.026 h(-1), P < 0.05). Apo E increased and apo A-I decreased in HDL, whereas PON-1 activity increased in proteinuric rabbits. Proteinuria was associated with an increased number of large HDL2b particles and a decreased number of small HDL3b and 3c. Proteinuria was also connected to an alteration in HDL subclass lipids, apolipoprotein content of HDL, high paraoxonase-1 activity, and a rise in the fractional catabolic rate of the [(131)I]-apo A-I.

No abstract

No abstract

No abstract

We conducted a case-control study in order to evaluate whether ABO gene polymorphisms were associated with a high risk of developing COVID-19 in a cohort of patients. Six ABO gene polymorphisms (rs651007 T/C, rs579459 T/C, rs495828 T/G, rs8176746 A/C, rs8176740 T/A, and rs512770 T/C) were determined using TaqMan genotyping assays in a group of 415 COVID-19 patients and 288 healthy controls. The distribution of rs651007 T/C, rs579459 T/C, rs495828 T/G, and rs8176746 A/C polymorphisms was similar in patients and healthy controls. Nonetheless, under co-dominant (OR = 1.89, pCCo-dominant = 6 × 10−6), recessive (OR = 1.98, pCRecessive = 1 × 10−4), and additive (OR = 1.36, pCAdditive = 3 × 10−3) models, the TT genotype of the rs8176740 T/A polymorphism increased the risk of developing COVID-19. In the same way, under co-dominant, recessive, and additive models, the TT genotype of the rs512770 T/C polymorphism was associated with a high risk of developing COVID-19 (OR = 1.87, pCCo-dominant = 2 × 10−3; OR = 1.87, pCRecessive = 5 × 10−4; and OR = 1.35, pCAdditive = 4 × 10−3, respectively). On the other hand, the GTC and GAT haplotypes were associated with a high risk of COVID-19 (OR = 5.45, pC = 1 × 10−6 and OR = 6.33, pC = 1 × 10−6, respectively). In addition, the rs8176740 TT genotype was associated with high-platelet plasma concentrations in patients with COVID-19. Our data suggested that the ABO rs512770 T/C and rs8176740 T/A polymorphisms increased the risk of developing COVID-19 and the plasma concentration of platelets.