Interaction between three stress-related gene polymorphisms and food addiction increases the risk to develop obesity in a sample of Mexican people attending a nutrition clinic.

Chronic stress exposure impacts negatively in individuals leading to food addiction, overweight or obesity. Stress-genes and their translation products are responsible for the responses of humans to adverse environments. Alterations in stress-genes expression or protein function may induce behaviors as compulsive eating of high-energy containing food, which decreases stress-induced negative feelings. However, chronic stress is not assessed in Mexican population. We analyzed here the association between polymorphisms of CRH, CRHR2 and glucocorticoids (GR, NR3C1) receptor genes with food addiction and obesity and overweight in Mexican patients of a Nutrition Clinic. We recruited 508 individuals of both genders, who accepted to participate in the study at their first visit to the clinic, obtaining their fat mass percentage and a blood sample for the genetic analysis. Participants answered the Yale's food addiction scale and were subjected to a Trier social test, as an acute stressful stimulus. Pre and post-test saliva samples were obtained to evaluate cortisol levels and adrenal axis' response to the acute stress. The 63% of participants classified as stressed (S); 6.5% of normal-weight individuals showed food-addiction, whereas 63% of participants with food-addiction were also stressed. The fat mass percentage was greater in stress-addiction than in stressed non-addiction participants. The best interaction model for obesity development risk comprehended the presence of polymorphisms of the three genes that in combination with food addiction increased the risk for developing obesity 2.8-4-fold. Thus, frequent stress exposure favors food-addiction, which along with genetic susceptibility seems to add up to Mexican obesity/overweight rates.

Effect of CRHR1 and CRHR2 gene polymorphisms and childhood trauma in suicide attempt.

Family, twin, and adoption studies have suggested that genetic factors might be involved in suicidal behavior. Corticotropin-releasing receptor type 1 (CRHR1) and 2 (CRHR2) genes play a key role in the activation and modulation of the hypothalamic-pituitary-adrenal (HPA) axis, which is considered a major stress regulator. Childhood trauma is an environmental risk factor associated with suicide attempt (SA) and it has been related to HPA axis dysregulation. This study aimed at analyzing the relationship of CRHR1 and CRHR2 genes with childhood trauma concerning the development of SA. In this study, we included 366 affective disorder patients. Among them, 183 patients had SA at least once and 183 had not SA. Information regarding SA and childhood trauma was obtained from medical records. Multifactor Dimensionality Reduction program was used to detect gene-environment interactions between CRHR1 (rs110402, rs242924, and rs16940665) and CRHR2 (rs2190242, rs2284217, and rs2014663) with childhood trauma in SA. The analysis showed an interaction of CRHR1 and CRHR2 with childhood trauma, thus conferring increased risk of having presented at least one SA (OR 7.44; 95% CI 4.58-12.07; p < 0.0001). In addition, we observed the following in the trauma subtypes analysis: physical negligence (OR 4.72; 95% CI 3.01-7.40; p < 0.0001), emotional abuse (OR 5.76; 95% CI 3.67-9.05; p < 0.0001), and sexual abuse (OR 5.70; 95% CI 3.62-8.97; p < 0.0001). Our results suggested that genetic variants of CRHR1 and CRHR2 genes in addition to physical negligence, and emotional and sexual abuse, contribute to increase risk of presented at least one SA.

"Exposure to the insecticides permethrin and malathion induces leukemia and lymphoma-associated gene aberrations in vitro".

Epidemiological studies have associated the exposure to permethrin and malathion with increased risk of leukemia and lymphoma. The aim of this study was to evaluate whether in vitro exposure to permethrin and malathion induces aberrations in genes involved in the etiology of these hematological malignancies. Genetic abnormalities in the IGH, KMT2A (MLL), ETV6 and RUNX1 genes, and aneuploidy induced by the in vitro exposure to permethrin and malathion (200µM, 24h), were analyzed by FISH in peripheral blood mononuclear cells (PBMCs). The gene fusions IGH-BCL2, KMT2A-AFF1 and ETV6-RUNX1 were further analyzed with nested RT-PCR in PBMCs, and in K562 cells exposed to acute and chronic treatments (0.1µM, 24h or every third day for two weeks) of insecticides. FISH analysis revealed that permethrin induces aneuploidy and structural alterations in IGH and KMT2A genes, and malathion induces breaks in KMT2A. RT-PCR detected ETV6-RUNX1 fusion in PBMCs acutely exposed to permethrin. Permethrin also induced ETV6-RUNX1 and IGH-BCL2 fusions in K562 cells, and malathion induced KMT2A-AFF1 and ETV6-RUNX1 fusions. Overall, we identified that both insecticides induce breaks and fusions in the studied genes, and permethrin induces aneuploidy. This study presents evidence of damage in cancer genes caused by these insecticides.