Association of HMOX1 and NQO1 Polymorphisms with Metabolic Syndrome Components.

Metabolic syndrome (MetS) is among the most important public health problems worldwide, and is recognized as a major risk factor for various illnesses, including type 2 diabetes mellitus, obesity, and cardiovascular diseases. Recently, oxidative stress has been suggested as part of MetS aetiology. The heme oxygenase 1 (HMOX1) and NADH:quinone oxidoreductase 1 (NQO1) genes are crucial mediators of cellular defence against oxidative stress. In the present study, we analysed the associations of HMOX1 (GT)n and NQO1 C609T polymorphisms with MetS and its components. Our study population comprised 735 Mexican Mestizos unrelated volunteers recruited from different tertiary health institutions from Mexico City. In order to know the HMOX1 (GT)n and NQO1 C609T allele frequencies in Amerindians, we included a population of 241 Amerindian native speakers. Their clinical and demographic data were recorded. The HMOX1 (GT)n polymorphism was genotyped using PCR and fluorescence technology. NQO1 C609T polymorphism genotyping was performed using TaqMan probes. Short allele (<25 GT repeats) of the HMOX1 polymorphism was associated with high systolic and diastolic blood pressure, and the T allele of the NQO1 C609T polymorphism was associated with increased triglyceride levels and decreased HDL-c levels, but only in individuals with MetS. This is the first study to analyse the association between MetS and genes involved in oxidative stress among Mexican Mestizos. Our data suggest that polymorphisms of HMOX1 and NQO1 genes are associated with a high risk of metabolic disorders, including high systolic and diastolic blood pressure, hypertriglyceridemia, and low HDL-c levels in Mexican Mestizo individuals

Characteristics of the Mexican Mestizo population.

<p>Age = average ± standard deviation.</p><p>HDL-c (< 40 men or < 50 mg/dL women),</p><p>Waist circumference (> 102 cm men or > 88 cm women).</p><p>Characteristics of the Mexican Mestizo population.</p

Genotype and allele frequencies of <i>HMOX1</i> (GT)<i>n</i> polymorphism in Mexican Mestizo individuals.

<p>MetS = Metabolic syndrome. Data are presented as frequency (sample size).</p><p><i>P</i> values were adjusted by age, BMI, gender, medicament status,</p><p>and Bonferroni correction.</p><p>Genotype and allele frequencies of <i>HMOX1</i> (GT)<i>n</i> polymorphism in Mexican Mestizo individuals.</p

Frequency distribution of <i>HMOX1</i> (GT)<i>n</i> polymorphism.

<p>The number of repeats in Amerindian population (white bar, n = 241), and Mestizo population (black bar, n = 735) are shown as percentage.</p

Genotype and allele frequencies of <i>HMOX1</i> and <i>NQO1</i> polymorphisms in Amerindian and Mestizo populations.

<p>Data are presented as frequency (sample size).</p><p><i>P</i> values were adjusted by Bonferroni correction.</p><p>Genotype and allele frequencies of <i>HMOX1</i> and <i>NQO1</i> polymorphisms in Amerindian and Mestizo populations.</p

Associations of <i>NQO1</i> C609T polymorphisms with components of metabolic syndrome.

<p>Comparisons were made relative to the CC genotype and C allele.</p><p>^aQuantitative analysis: beta = −1.8, <i>P</i> = 0.0008. <i>P</i> values were adjusted by age, BMI, gender, medicament status, and Bonferroni correction.</p><p>Associations of <i>NQO1</i> C609T polymorphisms with components of metabolic syndrome.</p

Associations of <i>HMOX1</i> (GT)<i>n</i> polymorphisms with components of metabolic syndrome.

<p>Comparisons were made relative to the LL genotype and L allele. Quantitative analysis, Beta value:</p><p>^<b>A</b> 1.6, <i>P</i> = 0.07.</p><p>^B 3.2, <i>P</i> = 0.009.</p><p>^<b>C</b>1.3, <i>P</i> = 0.03,</p><p>^<b>D</b> = 1.7, <i>P</i> = 0.04.</p><p><i>P</i> values were adjusted by age,</p><p>BMI, gender, medicament status, and Bonferroni correction.</p><p>Associations of <i>HMOX1</i> (GT)<i>n</i> polymorphisms with components of metabolic syndrome.</p

Combined dark matter searches towards dwarf spheroidal galaxies with Fermi-LAT, HAWC, H.E.S.S., MAGIC, and VERITAS

Cosmological and astrophysical observations suggest that 85\% of the total matter of the Universe is made of Dark Matter (DM). However, its nature remains one of the most challenging and fundamental open questions of particle physics. Assuming particle DM, this exotic form of matter cannot consist of Standard Model (SM) particles. Many models have been developed to attempt unraveling the nature of DM such as Weakly Interacting Massive Particles (WIMPs), the most favored particle candidates. WIMP annihilations and decay could produce SM particles which in turn hadronize and decay to give SM secondaries such as high energy $\gamma$ rays. In the framework of indirect DM search, observations of promising targets are used to search for signatures of DM annihilation. Among these, the dwarf spheroidal galaxies (dSphs) are commonly favored owing to their expected high DM content and negligible astrophysical background. In this work, we present the very first combination of 20 dSph observations, performed by the Fermi-LAT, HAWC, H.E.S.S., MAGIC, and VERITAS collaborations in order to maximize the sensitivity of DM searches and improve the current results. We use a joint maximum likelihood approach combining each experiment's individual analysis to derive more constraining upper limits on the WIMP DM self-annihilation cross-section as a function of DM particle mass. We present new DM constraints over the widest mass range ever reported, extending from 5 GeV to 100 TeV thanks to the combination of these five different $\gamma$-ray instruments