AXIN2-associated adenomatous colorectal polyposis

Abstract: Introduction Most cases of colorectal cancer (CRC) occur sporadically; however, ~3% to 6% of all CRCs are related to inherited syndromes, such as Lynch syndrome and familial adenomatous polyposis (FAP). The adenomatous polyposis coli (APC) andmutY DNA glycosylase (MUTYH) germline mutations are the main genetic causes related to colorectal polyposis. Nevertheless, in many cases mutations in these genes have not been identified. The aim of the present case report is to describe a rare case of genetic colorectal polyposis associated with the axis inhibition protein 2 (AXIN2) gene. Case Report: The first colonoscopy screening of a 61-year-old male patient with no known family history of CRC revealed ~ 50 colorectal polyps. A histological evaluation of the resected polyps showed low-grade tubular adenomas. Germline genetic testing through a multigene panel for cancer predisposition syndromes revealed a pathogenic variant in the AXIN2 gene. In addition to colorectal polyposis, the patient had mild features of ectodermal dysplasia: hypodontia, scant body hair, and onychodystrophy. Discussion: The AXIN2 gene acts as a negative regulator of the Wnt/β -catenin signaling pathway, which participates in development processes and cellular homeostasis. Further studies are needed to support the surveillance recommendations for carriers of the AXIN2 pathogenic variant. (AU)

Association of single nucleotide polymorphisms in AXIN2, BMP4, and IRF6 with Non-Syndromic Cleft Lip with or without Cleft Palate in a sample of the southeast Iranian population

Abstract Non-syndromic cleft lip with or without palate (NSCL/P) is a common congenital malformation worldwide, with complex etiology. It has been proposed that interaction of genes and environmental factors play a role in the predisposition to this disease. Objectives: The aim of this study was to examine the association between AXIN2 (axis inhibition protein 2) rs7224837, BMP4 (bone morphogenetic protein 4) rs17563, and IRF6 (interferon regulatory factor 6) rs861019 and 2235371 polymorphisms and NSCL/P in an Iranian population. Material and Methods: This case-control study was carried out on 132 unrelated NSCL/P patients and 156 healthy subjects. The variants were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: The findings suggest that BMP4 rs17563 polymorphism significantly decreased the risk of NSCL/P in codominant (OR=0.36, 95%CI=0.17-0.79, p=0.012, CT vs CC and OR=0.11, 95%CI=0.01-0.88, p = 0.019, TT vs CC), dominant (OR=0.30, 95%CI=0.15-0.62, p = 0.0007, CT+TT vs CC), recessive (OR=0.12, 95%CI=0.02-0.99, p = 0.023, TT vs CC+CT), overdominant (OR=0.39, 95%CI = 0.18-0.84, p=0.021, CT vs CC+TT), and allele (OR=0.28, 95%CI=0.15-0.55, p<0.0001, T vs C) inheritance models. Our findings did not support an association between AXIN2 rs7224837 and IRF6 rs861019 polymorphism and risk/protection of NSCL/P. The IRF6 2235371 variant was not polymorphic in our population. Conclusion: The results indicate that the BMP4 rs17563 variant is likely to confer a protective effect against the occurrence of NSCL/P in a sample of the southeast Iranian population.

Leisure-time physical activity and cardiometabolic risk among children and adolescents / Atividade física de lazer e risco cardiometabólico em crianças e adolescentes

OBJECTIVE: To assess the effect of Leisure-time physical activity (LTPA) on cardiometabolic risk by nutritional status in Mexican children and adolescents. METHODS: This was a cross-sectional study conducted with 1,309 participants aged between 5 and 17 years. Nutritional status was classified according to the BMI Z-score by age and gender. A previously validated questionnaire was used to evaluate LTPA; a cardiometabolic risk score was calculated. Multiple linear regression analysis was performed to assess the effect of LTPA on cardiometabolic risk. RESULTS: After adjusting for risk factors, mild LTPA were positively associated with cardiometabolic risk score (ßMildvsIntenseLTPA: 0.68; 95% CI: 0.18 to 1.18; pfortrend = 0.007). This association became stronger when estimated for overweight (ß MildvsIntenseLTPA: 1.24; 95% CI: 0.24 to 2.24; pfortrend = 0.015) and obese participants (ß MildvsIntenseLTPA: 1.02; 95% CI: 0.07 to 1.97; pfortrend= 0.045) CONCLUSION: Mild LTPA was positively associated with cardiometabolic risk in overweight and obese children and adolescents. Given the emerging childhood obesity epidemic in Mexico, these results may be useful in the design of strategies and programs to increase physical activity levels in order to achieve better health. .

OBJETIVO: Avaliar o efeito da prática de AFL sobre o risco cardiometabólico em crianças e adolescentes mexicanos de acordo com sua situação nutricional. MÉTODOS: Estudo transversal feito com 1.309 participantes de cinco a 17 anos. A situação nutricional foi classificada de acordo com o escore z de IMC por idade e sexo. Um questionário validado anteriormente foi usado para avaliar a AFL; foi calculado um escore de risco cardiometabólico. A análise de regressão linear múltipla foi feita para avaliar o efeito de AFL sobre o risco cardiometabólico. RESULTADOS: Após o ajuste de acordo com os fatores de risco, a AFL leve foi positivamente associada ao escore de risco cardiometabólico (ßAFLLevexIntensa: 0,68; IC 95%: 0,18 a 1,18; p paratendência = 0,007). Essa associação foi mais intensa quando estimada para participantes acima do peso (ßAFLLevexIntensa: 1,24; IC 95%: 0,24 a 2,24; p paratendência = 0,015) e obesos (ßAFLLevexIntensa: 1,02; IC 95%: 0,07 a 1,97; p paratendência = 0,045). CONCLUSÃO: A AFL leve foi positivamente associada ao escore de risco cardiometabólico em crianças e adolescentes acima do peso e obesos. Considerando a epidemia de obesidade infantil emergente no México, esses resultados poderão ser úteis na elaboração de estratégias e programas para aumentar os níveis de atividade física a fim de obter uma saúde melhor. .

PAX9 polymorphism and susceptibility to sporadic non-syndromic severe anodontia: a case-control study in southwest China

Our research aimed to look into the clinical traits and genetic mutations in sporadic non-syndromic anodontia and to gain insight into the role of mutations of PAX9, MSX1, AXIN2 and EDA in anodontia phenotypes, especially for the PAX9. Material and Methods The female proband and her family members from the ethnic Han families underwent complete oral examinations and received a retrospective review. Venous blood samples were obtained to screen variants in the PAX9, MSX1, AXIN2, and EDA genes. A case-control study was performed on 50 subjects with sporadic tooth agenesis (cases) and 100 healthy controls, which genotyped a PAX9 gene polymorphism (rs4904210). Results Intra-oral and panoramic radiographs revealed that the female proband had anodontia denoted by the complete absence of teeth in both the primary and secondary dentitions, while all her family members maintained normal dentitions. Detected in the female proband were variants of the PAX9 and AXIN2 including A240P (rs4904210) of the PAX9, c.148C>T (rs2240308), c.1365A>G (rs9915936) and c.1386C>T (rs1133683) of the AXIN2. The same variants were present in her unaffected younger brother. The PAX9 variations were in a different state in her parents. Mutations in the MSX1 and EDA genes were not identified. No significant diferences were found in the allele and genotype frequencies of the PAX9 polymorphism between the controls and the subjects with sporadic tooth agenesis. Conclusions These results suggest that the association of A240P with sporadic tooth agenesis still remains obscure, especially for different populations. The genotype/phenotype correlation in congenital anodontia should be verified. .