Our results suggest a previously unknown role of NKX2-5 in the pathogenesis of TD.

Objective: To identify risk factors for permanent and transient congenital hypothyroidism (CH). Design: A population-based case-control study was carried out by using the network created in Italy for the National Register of Infants with CH. Methods: Four controls were enrolled for each new CH infant; 173 cases and 690 controls were enrolled in 4 years. In order to distinguish among risk factors for permanent and transient CH, diagnosis was re-evaluated 3 years after enrolment when there was a suspicion of transient CH being present. Familial, maternal, neonatal and environmental influences were investigated. Results: An increased risk for permanent CH was detected in twins by a multivariate analysis (odds ratio (OR) ¼ 12.2, 95% confidence interval (CI): 2.4 -62.3). A statistically significant association with additional birth defects, female gender and gestational age .40 weeks was also confirmed. Although not significant, an increased risk of CH was observed among infants with a family history of thyroid diseases among parents (OR ¼ 1.9, 95% CI: 0.7-5.2). Maternal diabetes was also found to be slightly associated with permanent CH (OR ¼ 15.7, 95% CI: 0.9-523) in infants who were large for gestational age. With regard to transient CH, intrauterine growth retardation and preterm delivery were independent risk factors for this form of CH. Conclusion: This study showed that many risk factors contribute to the aetiology of CH. In particular, our results suggested a multifactorial origin of CH in which genetic and environmental factors play a role in the development of the disease. 153 765-773 European Journal of Endocrinology

Context Newborn screening program for congenital hypothyroidism (CH) adopting rescreening in at-risk neonates. Objectives To estimate the concordance rate for CH in twin pairs discordant at the first screening; to verify whether long-term follow-up of healthy cotwins belonging to CH discordant pairs may be useful to diagnose thyroid hypofunction during development; to evaluate the importance of genetic and environmental influences on liability to permanent and transient CH. Design and Patients Forty-seven screening discordant twin pairs were investigated. Proband was defined as the twin in the pair with a positive test at the first screening and a confirmed diagnosis of CH. Results Seven screening discordant twin pairs became concordant for CH within the first month of life (pairwise concordance of 14.9%) because seven screening negative cotwins showed high TSH values when retested. During long-term follow-up (range, 3 to 21 years), hypothyroidism was diagnosed in two monozygotic screening negative cotwins at the age of 9 months and 12 years, respectively. Furthermore, the twin analysis showed that 95% of liability to transient CH was explained by genetic factors and 5% by environmental (unshared) factors, whereas 64% of phenotypic variance of permanent CH was explained by common environmental factors (shared during the fetal life) and 36% by unshared environmental factors. Conclusions This study showed that the introduction of rescreening permits the diagnosis of CH in a greater number of twins. It also showed the importance of long-term follow-up in both twins in the pair, and the role of nongenetic factors in the etiology of permanent CH.

ABSTRACT. Venous thromboembolism (VTE) is an important cause of morbidity and mortality stemming from cardiovascular disease. It is a multifactorial disease caused by a combination of acquired risk factors, of which advanced age is the most significant, and genetic factors, including the variants FV G1691A, FII G20210A, and MTHFR C677T. We estimated the prevalence of these genomic variants in an elderly population of northeastern Brazil. The study included 188 elderly persons (65-93 years), of which 68 (36.2%) were men and 120 (63.8%) were women. Variants were detected by polymerase chain reaction-3699 FV G1691A, FII G20210A, and MTHFR C677T in the elderly ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 12 (3): 3698-3707 (2013) restriction fragment length polymorphism analysis, and subsequent electrophoresis on an 8% polyacrylamide gel stained with silver nitrate. The study population was in Hardy-Weinberg equilibrium for the 3 loci. Of the individuals analyzed, none carried variants of FV or FII (0%), and 24.7% had the MTHFR C677T polymorphism: 59 subjects (31.4%) were heterozygous (CT) and 17 subjects (9%) were homozygous (TT). Based on the analysis of these particular genes, we conclude that the study population does not present an increased risk for the development of VTE. Faced with a growing aging population worldwide, similar studies in other countries will help in the prevention of VTE in older individuals.

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