Mario Moraes

Phenotype–genotype profiles in Crohn's disease predicted by genetic markers in autophagy‐related genes (GOIA study II)

Background:About 70 loci are associated with susceptibility to Crohns disease (CD), particularly in pathways of innate immunity, autophagy, and pathogen recognition. Phenotype–genotype associations are inconsistent. Methods:CD susceptibility polymorphisms ATG16L1 rs2241880, ICAM1 rs5498, IL4 rs2070874, IL17F rs763780, IRGM rs13361189, ITLN1 rs2274910, LRRK2 rs11175593, and TLR4 rs4986790 were genotyped in a Portuguese population (511 CD patients, 626 controls) and assessed for association with CD clinical characteristics. Results:There is a significant association of CD with the single nucleotide polymorphisms (SNPs) in ATG16L1 (odds ratio [OR] 1.36 [1.15–1.60], P = 2.7 × 10−4 for allele G), IRGM (OR 1.56 [1.21–1.93], P = 3.9 × 10−4 for allele C), and ITLN1 (OR 1.55 [1.28–1.88], P = 4.9 × 10−6 for allele C). These SNPs are associated with ileal location (OR, respectively, 1.49, 1.52, and 1.70), ileocolonic location (OR, respectively, 1.31, 1.57, and 1.68), and involvement of the upper digestive tract (OR, respectively for ATG16L1 and IRGM, 1.96 and 1.95). The risk genotype GG in ATG16L1 is associated with patients who respond to steroids (OR 1.89), respond to immunosuppressants (OR 1.77), and to biologic therapy (OR 1.89). The SNPs in ITLN1 and IRGM are both associated with a positive response to biologic therapy. The risk for ileal, ileocolonic, and upper digestive tract locations increases with the number of risk alleles (OR for three alleles, respectively, 7.10, 3.54, and 12.07); the OR for positive response to biologic therapy is 3.66. Conclusions:A multilocus approach using autophagy-related genes provides insight into CD phenotype–genotype associations and genetic markers for predicting therapeutic responses.

Depresión materna postnatal y su repercusión en el neurodesarrollo infantil: estudio de cohorte

Introduction: Post partum depresion (DPP) is the most frequent psquiatric disorder in pregnant woman and it may affect the neurodevelopment of their offspring. Our goal was to analyze the association between maternal depressive symptoms at 6 months after birth and child’s neurodevelopmental disorders at 18 months-old, in a homogeneous population characterized by low socioeconomic and cultural level. Patients and Methods : A prospective cohort study was conducted. There were included 127 healthy postpartum women and their infants. A structured interview was performed which included patronymic data and family perception before discharge. Binomial monitoring took place at 6 months postpartum, when was applied the Beck test for depression and anxiety to mothers; children´s neurodevelopment at 18 month-old was evaluated by Lezine Revised Brunettest. Results: The sample consisted of 125 women and their children. The mean age was 24.5 year old (SD 6.02); 30.6% had completed less than 6 years of formal education. The incidence of moderate to severe postpartum depression at 6 months after birth was 20%. The overall development score mean was 73.52 (SD 8.06) in the depression population and 76.97 (SD 8.07) in the population without depression (p = 0.04). The development coefficient was 69.08 (SD: 10.35) in the depression population and 74.11 (SD 0.67) in the population without depression (p = 0.01). Conclusions: The incidence of moderate to severe DPP was 20%. Persistent DPP in a vulnerable socio-economic context has impact on child development.