Autonomic dysfunction is frequent in patients with fibromyalgia (FM). Heart rate variability analyses have demonstrated signs of ongoing sympathetic hyperactivity. Catecholamines are sympathetic neurotransmitters. Catechol-O-methyltransferase (COMT), an enzyme, is the major catecholamine-clearing pathway. There are several single-nucleotide polymorphisms (SNPs) in the COMT gene associated with the different catecholamine-clearing abilities of the COMT enzyme. These SNPs are in linkage disequilibrium and segregate as 'haplotypes'. Healthy females with a particular COMT gene haplotype (ACCG) producing a defective enzyme are more sensitive to painful stimuli. The objective of our study was to define whether women with FM, from two different countries (Mexico and Spain), have the COMT gene haplotypes that have been previously associated with greater sensitivity to pain. All the individuals in the study were female. Fifty-seven Mexican patients and 78 Spanish patients were compared with their respective healthy control groups. All participants filled out the Fibromyalgia Impact Questionnaire (FIQ). Six COMT SNPs (rs2097903, rs6269, rs4633, rs4818, rs4680, and rs165599) were genotyped from peripheral blood DNA. In Spanish patients, there was a significant association between three SNPs (rs6269, rs4818, and rs4680) and the presence of FM when compared with healthy controls. Moreover, in Spanish patients with the 'high pain sensitivity' haplotype (ACCG), the disease, as assessed by the FIQ, was more severe. By contrast, Mexican patients displayed only a weak association between rs6269 and rs165599, and some FIQ subscales. In our group of Spanish patients, there was an association between FM and the COMT haplotype previously associated with high pain sensitivity. This association was not observed in Mexican patients. Studies with a larger sample size are needed in order to verify or amend these preliminary results.

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.

Interleukin 35 (IL-35) is a heterodimeric cytokine involved in the development of atherosclerosis. The aim of the present study was to establish if the polymorphisms ofIL-12AandEBI3genes that encode the IL-35 subunits are associated with the development of premature coronary artery disease (CAD) in Mexican individuals. TheIL-12AandEBI3polymorphisms were determined in 1162 patients with premature CAD and 873 controls. Under different models, theEBI3rs428253 (OR = 0.831,Padd= 0.036; OR = 0.614,Prec= 0.033; OR = 0.591,Pcod2= 0.027) andIL-12Ars2243115 (OR = 0.674,Padd= 0.010; OR = 0.676,Pdom= 0.014; OR = 0.698,Phet= 0.027; OR = 0.694,Pcod1= 0.024) polymorphisms were associated with decreased risk of developing premature CAD. Some polymorphisms were associated with clinical and metabolic parameters. Significant different levels of IL-35 were observed inEBI3rs4740 and rs4905 genotypes only in the group of healthy controls. In summary, our study suggests that theEBI3andIL-12Apolymorphisms play an important role in decreasing the risk of developing premature CAD; it also demonstrates the relationship of theEBI3rs4740 and rs4905 genotypes with IL-35 levels in healthy individuals.

SARS-CoV-2 uses the ACE2 receptor and the cellular protease TMPRSS2 for entry into target cells. The present study aimed to establish if the TMPRSS2 polymorphisms are associated with COVID-19 disease. The study included 609 patients with COVID-19 confirmed by RT-PCR test and 291 individuals negative for the SARS-CoV-2 infection confirmed by RT-PCR test and without antibodies anti-SARS-CoV-2. Four TMPRSS2 polymorphisms (rs12329760, rs2298659, rs456298, and rs462574) were determined using the 5′exonuclease TaqMan assays. Under different inheritance models, the rs2298659 (p_codominant2 = 0.018, p_recessive = 0.006, p_additive = 0.019), rs456298 (p_codominant1 = 0.014, p_codominant2 = 0.004; p_dominant = 0.009, p_recessive = 0.004, p_additive = 0.0009), and rs462574 (p_codominant1 = 0.017, p_codominant2 = 0.004, p_dominant = 0.041, p_recessive = 0.002, p_additive = 0.003) polymorphisms were associated with high risk of developing COVID-19. Two risks (ATGC and GAAC) and two protectives (GAGC and GAGT) haplotypes were detected. High levels of lactic acid dehydrogenase (LDH) were observed in patients with the rs462574AA and rs456298TT genotypes (p = 0.005 and p = 0.020, respectively), whereas, high heart rate was present in patients with the rs462574AA genotype (p = 0.028). Our data suggest that the rs2298659, rs456298, and rs462574 polymorphisms independently and as haplotypes are associated with the risk of COVID-19. The rs456298 and rs462574 genotypes are related to high levels of LDH and heart rate.

Background: Cytokines are a group of polypeptides with an important role in the inflammatory response. It has been suggested that certain polymorphisms located in several cytokine genes are associated with different diseases. The aim of the present study was to establish the gene frequency of 13 polymorphisms of the IL-1RN , IL-6 , IL-10 , INF-γ , and TNF-α genes in a Mexican population. These polymorphisms have been reported in several populations, with important variation in frequency according to the studied population. Methods: Thirteen polymorphisms (rs419598, rs315951, rs2234663, rs3811058, rs1800796, rs2069827, rs1800896, rs1800871, rs1800872, rs1800629, rs2069709, rs2069710, and rs361525) were analyzed by 5′ exonuclease TaqMan genotyping assays in a group of 248 healthy unrelated Mexican individuals. Results: The results obtained showed that the studied Mexican population presents significant differences ( p <0.05) in the distribution of the IL1RN (rs419598, rs315951, and and rs2234663), IL1F10 (rs3811058), IL6 (rs1800796, rs2069827), IL10 (rs1800896, rs1800871, and rs1800872), and TNF-α (rs1800629) polymorphisms when compared to Caucasian, Asian, and African populations. Conclusions: In summary, the distribution of the IL-1RN , IL-6 , IL-10 , and TNF-α cytokine gene polymorphisms distinguishes the studied Mexican population from other groups. Since the alleles of these cytokines are associated with the development of several inflammatory diseases, knowledge of the distribution of these alleles in the studied Mexican population could be helpful to understand their true role as a genetic susceptibility marker in this population.