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.

Sequence analysis of five exons of SLC6A4 gene in Mexican patients with anorexia nervosa and bulimia nervosa.

BACKGROUND: Accumulating evidence indicates that alterations in the serotonin system are related to changes in eating behavior. The serotonin transporter is encoded by the SLC6A4 gene and has been an interesting candidate for anorexia nervosa- restrictive type (AN-R) and bulimia nervosa (BN). Interestingly, functional variants have been identified in the coding region that could contribute to understand the role of this gene in eating disorders. The aim was to identify genetic variants in five exons of SLC6A4 gene using Sanger-sequencing in anorexia nervosa-restrictive and bulimia nervosa patients, and a control group. METHOD: The sample consisted of 86 patients and 50 control subjects. We obtained DNA samples from all subjects and performed Sanger-sequence analysis of the 1, 2, 3, 8 and 9 exons. The sequences were compared with the reference sequence of the SLC6A4 gene. RESULTS: The sequence analysis of the five exons of the gene identified several variants. In the AN-R, we observed two novel variants (g.130delA and c.1740G > A), three synonymous variants (rs57172732, rs55908624, rs74478645) and a missense variant (L90F) reporting a probably deleterious and damaging variant. In BN, we identified two novel variants (g.295C > G and c.1725G > A), and the non-synonymous (rs28914832/I425V), reported as benign. Interestingly, we observed the 425V variant in three patients in the BN, variant that previously was reported in patients with a spectrum obsessive-compulsive disorder. CONCLUSION: The results of our study suggest that variants of the SLC6A4 gene are related with a possible damaging or gain-of-function and may be involved in the susceptibility to AN-R and BN patients. However, the present findings should be considered as preliminary until replicated in large samples.