A genome-wide association study identifies novel gene associations with facial skin wrinkling and mole count in Latin Americans.

BACKGROUND: Genome-wide association studies (GWASs) have identified genes influencing skin ageing and mole count in Europeans, but little is known about the relevance of these (or other genes) in non-Europeans. OBJECTIVES: To conduct a GWAS for facial skin ageing and mole count in adults < 40 years old, of mixed European, Native American and African ancestry, recruited in Latin America. METHODS: Skin ageing and mole count scores were obtained from facial photographs of over 6000 individuals. After quality control checks, three wrinkling traits and mole count were retained for genetic analyses. DNA samples were genotyped with Illumina's HumanOmniExpress chip. Association testing was performed on around 8 703 729 single-nucleotide polymorphisms (SNPs) across the autosomal genome. RESULTS: Genome-wide significant association was observed at four genome regions: two were associated with wrinkling (in 1p13·3 and 21q21·2), one with mole count (in 1q32·3) and one with both wrinkling and mole count (in 5p13·2). Associated SNPs in 5p13·2 and in 1p13·3 are intronic within SLC45A2 and VAV3, respectively, while SNPs in 1q32·3 are near the SLC30A1 gene, and those in 21q21·2 occur in a gene desert. Analyses of SNPs in IRF4 and MC1R are consistent with a role of these genes in skin ageing. CONCLUSIONS: We replicate the association of wrinkling with variants in SLC45A2, IRF4 and MC1R reported in Europeans. We identify VAV3 and SLC30A1 as two novel candidate genes impacting on wrinkling and mole count, respectively. We provide the first evidence that SLC45A2 influences mole count, in addition to variants in this gene affecting melanoma risk in Europeans.

Left-sided infective endocarditis in patients with liver cirrhosis.

OBJECTIVE: To evaluate the course of left-sided infective endocarditis (LsIE) in patients with liver cirrhosis (LC) analyzing its influence on mortality and the impact of surgery. METHODS: Prospective cohort study, conducted from 1984 to 2013 in 26 Spanish hospitals. RESULTS: A total of 3.136 patients with LsIE were enrolled and 308 had LC: 151 Child-Pugh A, 103 B, 34 C and 20 were excluded because of unknown stage. Mortality was significantly higher in the patients with LsIE and LC (42.5% vs. 28.4%; p < 0.01) and this condition was in general an independent worse factor for outcome (HR 1.51, 95% CI: 1.23-1.85; p < 0.001). However, patients in stage A had similar mortality to patients without cirrhosis (31.8% vs. 28.4% p = NS) and in this stage heart surgery had a protective effect (28% in operated patients vs. 60% in non-operated when it was indicated). Mortality was significantly higher in stages B (52.4%) and C (52.9%) and the prognosis was better for patients in stage B who underwent surgery immediately (mortality 50%) compared to those where surgery was delayed (58%) or not performed (74%). Only one patient in stage C underwent surgery. CONCLUSIONS: Patients with liver cirrhosis and infective endocarditis have a poorer prognosis only in stages B and C. Early surgery must be performed in stages A and although in selected patients in stage B when indicated.

High twinning rate in Cândido Godói: a new role for p53 in human fertility.

BACKGROUND: Cândido Godói (CG) is a small town in South Brazil, which has the highest prevalence of twin births in Brazil. Recently, a number of studies have shown that p53 plays an important role in reproduction through blastocyst implantation and intra utero embryo survival. Thus, gene polymorphisms in the p53 pathway were investigated in this population. METHODS: Single nucleotide polymorphisms from five genes in the p53 pathway were investigated, as well as background characteristics of 42 mothers of twins (cases) and 101 mothers of singletons (controls), all residents from CG. RESULTS: Mothers of twins have higher number of pregnancies and higher frequencies of P72 allele at TP53 and T allele at MDM4 genes compared with controls. Logistic regression shows that both TP53 and number of pregnancies maintained their association with twinning (P =0.004 and P =0.002, respectively), with TP53 having a higher odds ratio than number of pregnancies (2.73 versus 1.70, respectively). No interactive effect between TP53 and MDM4 (P =0.966) is observed. As expected, mothers of twins have three times more cases of cancer in their first-degree relatives than control mothers (P =0.011). CONCLUSIONS: Our results suggest that the P72 allele of TP53 is a strong risk factor for twinning in CG, while the number of pregnancies and the T allele at MDM4 may represent weaker risk factors. These two alleles are associated with infertility, but the anti-apoptotic effect of low levels of p53 in general, and of the P72 allele in particular, may play a role after implantation, enhancing the chance for a double pregnancy to succeed to term.

[Pericardial tamponade and carcinomatous lymphangitis as primary manifestation of lung neoplasm]. / Taponamiento pericárdico y linfangitis carcinomatosa como primera manifestación de neoplasia pulmonar.

Cardiac tamponade (CT) and Carcinomatous lymphangitis (CL) association as an initial clinical presentation of a neoplasm is very uncommon, creating diagnosis difficulties in the patient first evaluation. This paper reports one case of a male who was admitted in Emergency Department with clinical and radiological findings of heart failure. Following studies showed CT and CL secondary to a bronchial adenocarcinoma. Differential diagnosis is really important for its associated therapeutic implications because of the CT hemodynamic worsening situation due to the diuretic and vasodilators used in the treatment of heart failure. An echocardiography should be done because it is very useful for the initial evaluation of a heart failure of obscure origin.

[Impact of arterial hypertension on the central nervous system]. / Repercusión de la hipertensión arterial sobre el sistema nervioso central.

Cerebrovascular diseases (CVD) entail high costs associated to therapies, hospitalizations and disabilities. Arterial hypertension (AHT) is the major modifiable risk factor for the development of all types of CVDs (cerebrovascular accidents, vascular dementias, etc.). The increase of arterial pressure causes functional and anatomical changes in the cerebral circulation which facilitate the development of CVDs. The time of evolution and the severity of the AHT, as well as the associated vascular risk factors, will determine its impact on the central nervous system.

[Atrial fibrillation and cerebral infarct]. / Fibrilación auricular e infarto cerebral.

The importance of atrial fibrillation (AF) as a risk factor (RF) for cerebral infarction (CI) is well-known. It is probably caused by cardiac embolism but other explanations can also justify this association. Our aim was to analyse the features of the patients with CI and AF and sinus rhythm (SR), as well as to form hypotheses as regards the pathogenesis. 250 patients with CI, 204 in RS and 46 in AF (31 non-valvular and 15 associated to a valvular disease) were studied, analysing the prevalence of RF and initial blood tests. The group of patients with valvular AF of probably embolic mechanism had a minor prevalence of RF (hypertension, diabetes, smoking, alcoholism) but higher mortality. The group with non-valvular AF, had a lower RF prevalence compared to the SR group (non-embolic mechanism), without statistical significance and with a similar mortality rate. We concluded that the atherothrombotic mechanism can be the cause of a considerable proportion of CI in patients with non-valvular AF.

[Pulmonary fibrosis and autoimmune manifestations. A diagnostic problem]. / Fibrosis pulmonar y manifestaciones autoinmunes. Un problema diagnóstico.

A case of 54-year-old male who, during the development of a pulmonary fibrosis, showed extrapulmonary autoimmune symptoms (polyarthritis and hemolytic anemia), is presented. The antinuclear antibodies and rheumatoid factor positives have been described in up to 30% of the idiopathic pulmonary fibrosis, complicating the differential diagnosis with lung fibrosis caused by alterations of connective tissue. We discuss the prognosis and treatment of this difficult diagnosis.