ATP5H/KCTD2 locus is associated with Alzheimer's disease risk.

To identify loci associated with Alzheimer disease, we conducted a three-stage analysis using existing genome-wide association studies (GWAS) and genotyping in a new sample. In Stage I, all suggestive single-nucleotide polymorphisms (at P<0.001) in a previously reported GWAS of seven independent studies (8082 Alzheimer's disease (AD) cases; 12 040 controls) were selected, and in Stage II these were examined in an in silico analysis within the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium GWAS (1367 cases and 12904 controls). Six novel signals reaching P<5 × 10(-6) were genotyped in an independent Stage III sample (the Fundació ACE data set) of 2200 sporadic AD patients and 2301 controls. We identified a novel association with AD in the adenosine triphosphate (ATP) synthase, H+ transporting, mitochondrial F0 (ATP5H)/Potassium channel tetramerization domain-containing protein 2 (KCTD2) locus, which reached genome-wide significance in the combined discovery and genotyping sample (rs11870474, odds ratio (OR)=1.58, P=2.6 × 10(-7) in discovery and OR=1.43, P=0.004 in Fundació ACE data set; combined OR=1.53, P=4.7 × 10(-9)). This ATP5H/KCTD2 locus has an important function in mitochondrial energy production and neuronal hyperpolarization during cellular stress conditions, such as hypoxia or glucose deprivation.

Whole-genome conditional two-locus analysis identifies novel candidate genes for late-onset Parkinson's disease.

Whole-genome epistasis analysis may add a new layer of knowledge to whole-genome association studies, permitting the identification of new candidate genes which are completely transparent during conventional single-locus analysis. We present the first whole-genome conditional two-locus analysis in Parkinson's disease (PD). We scanned the entire genome and selected markers that interacted with a set of well-known loci previously associated to PD (SNCA, Parkin, LRRK2, UCHL1, DJ-1, PINK and MAPT). Our work describes several loci potentially related to PD risk which interact with SNCA, PARK1 and LRRK2 markers. We propose conditional whole-genome two-locus association analysis as a valuable method that might be helpful in re-analysing and re-interpreting data from whole-genome association studies.

Control de la obesidad infantil en atención primaria / Control of childhood obesity in Primary Care

Objetivos: Valorar la efectividad de un programa de promoción de hábitos alimentarios correctos y fomento de actividad física, para reducir la obesidad y el sobrepeso en un cupo pediátrico. Material y métodos: Diseño: estudio casi experimental antes y después. Ámbito: atención primaria. Sujetos: 611 niños de 2-13 años de edad, con sobrepeso u obesidad en un cupo pediátrico, entre 2005 y 2007. Intervenciones: promoción de actividad física y hábitos saludables. Variables: edad, sexo, antecedentes familiares de primer grado de obesidad, índice de masa corporal (IMC), analítica (perfil lipídico, hormona tiroestimulante, hemograma, metabolismo del hierro). Análisis estadístico: parámetros descriptivos de tendencia central y distribución de frecuencias. Contraste de hipótesis mediante la prueba de la t de Student y la c2. Resultados: La prevalencia de obesidad o sobrepeso fue del 12,11% (49 y 25 casos diagnosticados de obesidad y sobrepeso, respectivamente). El 73,6% de los niños obesos tenían antecedentes familiares de primer grado de sobrepeso u obesidad (p <0,01). A los dos años, en el 43,47% de los niños incluidos en el estudio el IMC se redujo o se estabilizó (1,94; intervalo de confianza del 95%: 1,17-2,70). A los dos años, el 4% de los niños que inicialmente tenían sobrepeso fueron categorizados como normopeso y el 52,3% de los obesos fueron categorizados como con sobrepeso (p <0,001). Conclusiones: La actuación del pediatra de atención primaria promoviendo la actividad física y la alimentación saludable, con controles de peso y talla periódicos, reduce los niveles de obesidad o sobrepeso en la población infantil. Es necesario identificar y abordar precozmente a los hijos de padres obesos (AU)

Objectives: To evaluate the effectiveness of a program to promote proper eating habits and physical activity to reduce obesity and overweight in a pediatric quota. Materials and methods: Design: quasi before and after. Setting: Primary Care. Subjects: 611 children between 2 and 13 years old, overweight or obesity in a pediatric quota between 2005 and 2007. Interventions: Promoting physical activity and food healthy habits. Variables: age, sex, family history of first degree of obesity, body mass index (BMI), analytical (lipid profile, TSH, blood, iron metabolism). Statistical Analysis: descriptive parameters of central tendency and distribution of frequencies. Student’s test and chi-square test. Results: The prevalence of overweight or obesity was12,11% (49 and 25 cases diagnosed of obesity and overweight respectively). 73,6% of the obese children had a family history of first degree of overweight or obesity (p <0,01). At the end of two years the BMI of 43,47% of children decreased or stabilized (1,94 Kg/m2; 95% CI 1,17-2,70); the 4,0% of children diagnosed of overweight initially, were normoweight; the 52,3% of children diagnosed of obesity initially, were overweight (p<0,001).Conclusions: The performance of primary care pediatrician promoting physical activity and healthy eating, weight and height continuous measurements, reduces levels of overweight or obesity in children. It is necessary to identify and to tackle early the children of obese parents (AU)

Analysis of CXCL12 3'UTR G>A polymorphism in colorectal cancer.

Colorectal cancer is one of the most prevalent cancers in developed countries. However, the genetic factors influencing its appearance remain far from being fully characterized. Recently, a G>A functional transition mapping the 3' untranslated region of the CXCL12 gene (rs1801157) has been found to be under-represented among rectal cancer patients when compared to colon cancer patients from a Swedish series. Here we present the results from an independent analysis of CXCL12 rs1801157 in a larger CRC series of Spanish origin in order to analyse the robustness of this association within a different European population. No significant difference was observed between controls and colon or rectal cancer patients. We were also unable to find a correlation between rs1801157 and different prognostic markers such as metastasis development or disease-free survival time. The epidemiologic data involving CXCL12 rs1801157 in colorectal cancer risk are discussed.

Molecular analysis of estrogen receptor alpha gene AGATA haplotype and SNP12 in European populations: potential protective effect for cryptorchidism and lack of association with male infertility.

BACKGROUND: A specific haplotype (AGATA) in the estrogen receptor alpha (ER1) gene was recently described as a new risk factor for cryptorchidism in the Japanese population. In this ethnic group, single-nucleotide polymorphism 12 (SNP12) was concluded to be the tag SNP for the AGATA haplotype. MATERIALS AND METHODS: A large group of patients (total number=335) and controls (total number=567) of two Caucasian populations were analysed for the AGATA haplotype and SNP12 to verify whether this genetic variant and its tag SNP were associated with cryptorchidism or with severe spermatogenic failure. RESULTS: We confirm that SNP12 is the tag SNP for the AGATA haplotype also in Caucasians. However, in contrast with the Japanese population we found a protective effect for ESR1 SNP12 on cryptorchidism in the Italian population. No association between SNP12 and severe spermatogenic disturbances was observed. CONCLUSIONS: The observed associations (although with opposite effect) with cryptorchidism encourage future studies on independent cases and controls from different ethnic and geographic origins. On the other hand, in contrast with other ESR1 polymorphisms, SNP12 polymorphism is not associated with severe male factor infertility in two independent European population.

Association of genetic markers within the KIT and KITLG genes with human male infertility.

BACKGROUND: There is much evidence involving the KIT tyrosine kinase receptor and its ligand KITLG in the survival and proliferation of germ cells. Animal models and functional studies in humans suggest that this signalling pathway plays a role in male infertility. METHODS: We studied three and two single-nucleotide polymorphisms (SNPs) (rs3819392, rs3134885, rs2237012, rs10506957 and rs995030) located within the genomic region of the KIT and KITLG genes, respectively. A total of 167 idiopathic infertile men (sperm counts <5 million spz/ml) and 465 unrelated healthy controls from the same geographical region were genotyped for these SNPs. RESULTS: We found a statistically significant association of the rs3819392 polymorphism, which is located within the KIT gene, with idiopathic male infertility. In addition, a deviation from the Hardy-Weinberg equilibrium (HWE) law was observed for rs10506957 polymorphism within the KITLG gene only in the infertile group. CONCLUSIONS: Our data indicate that the KIT/KITLG system may be involved in a low sperm count trait in humans.

Specific haplotypes of the CALPAIN-5 gene are associated with polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of reproductive age. The aim of the present study was to investigate the role of CALPAIN-5 (CAPN5) gene in PCOS susceptibility. METHODS: We analysed four intronic polymorphisms of the CAPN5 gene in 148 well-characterized women with PCOS and 606 unrelated controls. We performed a case-control study and an intracohort analysis of clinical characteristics associated with PCOS. RESULTS: Analysis of haplotypes distribution between PCOS population compared to controls showed a strong deviation (P = 0.00029). The haplotypes GGCA and GGTG were overrepresented in PCOS patients (P = 0.009 and P = 0.001, respectively). In addition, we identified several CAPN5 haplotypes associated with phenotypic differences observed between PCOS patients, such as the presence of obesity (P = 0.02), cardiovascular complications (P = 0.02), familial antecedents of obesity (P = 0.003) and of hypertension (P = 0.007) and type 2 diabetes mellitus aggregation (P = 0.04). CONCLUSIONS: These results suggest a role of CAPN5 gene in PCOS susceptibility in humans. Moreover, novel candidate risk alleles have been identified, within CAPN5 gene, which could be associated with important phenotypic and prognosis differences observed in PCOS patients.