Catechol-O-methyltransferase gene haplotypes in Mexican and Spanish patients with fibromyalgia

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

Association of Nuclear Factor-Erythroid 2-Related Factor 2, Thioredoxin Interacting Protein, and Heme Oxygenase-1 Gene Polymorphisms with Diabetes and Obesity in Mexican Patients

The nuclear factor-erythroid 2- (NF-E2-) related factor 2 (Nrf2) is abated and its ability to reduce oxidative stress is impaired in type 2 diabetes and obesity. Thus, the aim of this study was to explore if polymorphisms in Nrf2 and target genes are associated with diabetes and obesity in Mexican mestizo subjects. The rs1800566 of NAD(P)H:quinone oxidoreductase 1 (NQO1) gene, rs7211 of thioredoxin interacting protein (TXNIP) gene, rs2071749 of heme oxygenase-1 (HMOX1) gene, and the rs6721961 and the rs2364723 from Nrf2 gene were genotyped in 627 diabetic subjects and 1020 controls. The results showed that the rs7211 polymorphism is a protective factor against obesity in nondiabetic subjects (CC + CT versus TT, OR = 0.40, P=0.005) and in women (CC versus CT + TT, OR = 0.7, P=0.016). TT carriers had lower high-density lipoprotein cholesterol levels and lower body mass index. The rs2071749 was positively associated with obesity (AA versus AG + GG, OR = 1.25, P=0.026). Finally, the rs6721961 was negatively associated with diabetes in men (CC versus CA + AA, OR = 0.62, P=0.003). AA carriers showed lower glucose concentrations. No association was found for rs1800566 and rs2364723 polymorphisms. In conclusion, the presence of Nrf2 and related genes polymorphisms are associated with diabetes and obesity in Mexican patients

Increased carotid intima-media thickness and cardiometabolic risk factors are associated with IL-6 gene polymorphisms in Mexican individuals: The Genetics of Atherosclerotic Disease Mexican study

Interleukin 6 (IL-6) is a cytokine implicated in the development of atherosclerosis. This study aimed to determine the association of three IL-6 gene polymorphisms with increased carotid intima-media thickness (CIMT) and cardiometabolic risk factors. Three IL-6 polymorphisms (rs1800795, rs2069827, and rs1800796) were analyzed in 178 individuals with increased CIMT (CIMT ≥ 75th percentile) and 906 individuals without increased CIMT (CIMT < 75th percentile). Logistic regression, adjusted for confounding variables, was employed to assess the associations. The rs1800796 polymorphism was significantly associated with an elevated risk of increased CIMT (OR = 1.354, Padditive = 0.016; OR = 1.803, Precessive = 0.014; OR = 1.989, Pcodominant2 = 0.008). One haplotype (GCG) correlated with a higher risk of increased CIMT (OR = 1.288; P = 0.008), while another (GGG) demonstrated a reduced risk (OR = 0.773; P = 0.006). In individuals without increased CIMT, the rs2069827 polymorphism was associated with low risks of central obesity, hypoalphalipoproteinemia, and a low risk of presenting with high levels of total cholesterol (TC), non-high-density lipoprotein cholesterol (non-HDL-C), low-density lipoprotein cholesterol (LDL-C) /HDL-C index, apolipoprotein B, and gamma-glutamyl transpeptidase. The rs1800796 polymorphism was associated with a low risk of adipose tissue insulin resistance, and the rs1800795 was associated with a minimal risk of central obesity and hypoalphalipoproteinemia. Among those with increased CIMT, the rs2069827 was associated with low risks of central obesity, hypertriglyceridemia, metabolic syndrome, and a high triglyceride (TG)/HDL-C index, while rs1800796 was associated with a low risk of fatty liver. Similar IL-6 concentrations were observed in both individuals with and without increased CIMT. In conclusion, the rs1800796 polymorphism is associated with increased CIMT, while the rs2069827 and rs1800795 are linked to cardiovascular risk factors

Dietary fat and carbohydrate modulate the effect of the ATP-binding cassette A1 (ABCA1) R230C variant on metabolic risk parameters in premenopausal women from the Genetics of Atherosclerotic Disease (GEA) Study

Table S1. Demographic characteristics of the population. Table S2. Comparison of biochemical parameters stratified by gender and menopausal status. Table 3. Correlation between metabolic parameters and dietary macronutrients according to ABCA1/R230C genotypes in premenopausal women. Table S4. Comparison of biochemical parameters stratified by ABCA1/R230C genotypes in the study population and premenopausal women. Table 5. Comparison of biochemical parameters stratified by ABCA1/R230C genotypes and carbohydrate percentage tertiles in premenopausal women. Table 6. Comparison of biochemical parameters stratified by ABCA1/R230C genotypes and fat percentage tertiles in premenopausal women. (DOCX 162 kb

ELANE rs17223045C/T and rs3761007G/A variants: Protective factors against COVID-19

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for causing coronavirus disease 2019 (COVID-19). The development and severity of this infectious disease is influenced by a combination of environmental and genetic factors. Angiotensin-converting enzyme 2 (ACE2) facilitates SARS-CoV-2 entry into human cells, with transmembrane serine protease 2 (TMPRSS2) playing a crucial role in S protein priming. Other proteases, such as cathepsin L and elastase, neutrophil-expressed (ELANE), have the capability to prime the S protein and contribute to SARS-CoV-2 infection. ELANE variants have not been previously examined in COVID-19 patients. We aimed to assess the association of single nucleotide variants (SNVs) within ELANE with COVID-19 and biochemical markers. The study included 319 SARS-CoV-2-infected patients and 288 controls. Genotyping of ELANE rs17216663C/T (Pro257Leu), rs17223045C/T (As1n30Asn), and rs3761007G/A was conducted using a 5'-nuclease allelic discrimination assay (TaqMan assay). Our findings indicate that ELANE rs17223045C/T (C vs T: odds ratio [OR] 0.08, P = 0.005, and CC vs CT: OR 0.08, P = 0.005) and rs3761007G/A (G vs A: OR 0.38, P = 0.009, and GG vs GA: OR 0.40, P = 0.008) confer protection against COVID-19. However, these variants were not associated with biochemical markers. In conclusion, our data suggests that ELANE rs17223045C/T and rs3761007G/A SNVs may play a protective role against COVID-19

A SCN9A gene-encoded dorsal root ganglia sodium channel polymorphism associated with severe fibromyalgia

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>The frequency of the rs6754031 polymorphism was significantly different in both groups (<it>P </it>= 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; <it>P </it>= 0.002) and the TT genotype (median = 71; percentile 25/75 = 64/77; <it>P </it>= 0.001).</p> <p>Conclusion</p> <p>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.</p

HLA Class I and Class II Conserved Extended Haplotypes and Their Fragments or Blocks in Mexicans: Implications for the Study of Genetic Diversity in Admixed Populations

Major histocompatibility complex (MHC) genes are highly polymorphic and informative in disease association, transplantation, and population genetics studies with particular importance in the understanding of human population diversity and evolution. The aim of this study was to describe the HLA diversity in Mexican admixed individuals. We studied the polymorphism of MHC class I (HLA-A, -B, -C), and class II (HLA-DRB1, -DQB1) genes using high-resolution sequence based typing (SBT) method and we structured the blocks and conserved extended haplotypes (CEHs) in 234 non-related admixed Mexican individuals (468 haplotypes) by a maximum likelihood method. We found that HLA blocks and CEHs are primarily from Amerindian and Caucasian origin, with smaller participation of African and recent Asian ancestry, demonstrating a great diversity of HLA blocks and CEHs in Mexicans from the central area of Mexico. We also analyzed the degree of admixture in this group using short tandem repeats (STRs) and HLA-B that correlated with the frequency of most probable ancestral HLA-C/−B and -DRB1/−DQB1 blocks and CEHs. Our results contribute to the analysis of the diversity and ancestral contribution of HLA class I and HLA class II alleles and haplotypes of Mexican admixed individuals from Mexico City. This work will help as a reference to improve future studies in Mexicans regarding allotransplantation, immune responses and disease associations

ABO gene polymorphisms are associated with acute coronary syndrome and with plasma concentration of HDL-cholesterol and triglycerides

The role of ABO gene polymorphisms in acute coronary syndrome (ACS) and lipid metabolism is increasingly recognized. We investigated whether ABO gene polymorphisms are significantly associated with ACS and the plasma lipid profile. Six ABO gene polymorphisms (rs651007 T/C, rs579459 T/C, rs495928 T/C, rs8176746 T/G, rs8176740 A/T, and rs512770 T/C) were determined by 5’exonuclease TaqMan assays in 611 patients with ACS and 676 healthy controls. The results demonstrated that the rs8176746 T allele was associated with a lower risk of ACS under the co-dominant, dominant, recessive, over-dominant, and additive models (P = 0.0004, P = 0.0002, P = 0.039,  P = 0.0009, and P = 0.0001, respectively). Furthermore, under co-dominant, dominant, and additive models, the rs8176740 A allele was associated with a lower risk of ACS (P = 0.041, P = 0.022, and P = 0.039, respectively). On the other hand, the rs579459 C allele was associated with a lower risk of ACS under the dominant, over-dominant, and additive models (P = 0.025, P = 0.035, and P = 0.037, respectively). In a subanalysis performed with the control group, rs8176746 T and rs8176740 A alleles were associated with low systolic blood pressure and with both high high-density lipoprotein-cholesterol (HDL-C) and low triglyceride plasma concentrations, respectively. In conclusion, ABO gene polymorphisms were associated with a lower risk of ACS, and lower systolic blood pressure and plasma lipid levels, suggesting a causal relationship between ABO blood groups and the incidence of ACS