Paired-liked homeodomain transcription factor 2 gene polymorphism associated with interval defect congenital heart disease / 中华实用儿科临床杂志

Objective To investigate the correlation between heart development related genes paired-liked homeodomain transcription factor 2 (PITX2) and interval defect congenital heart disease (CHD).Methods To target the investigated single nucleotide polymorphisms (SNPs) by means of dbSNPs data base of National Center of Biotechnology Information(NCBI) website and online bioinformatics software,SNPper.To compared SNPs using 30 interval defect CHD patients and 30 healthy children as control group.Venous blood were collected to detect PITX2 DNA sequencing,then new SNPs were explored.Statistic differences of alleles and genotype frequency distribution between case group and control group were analyzed sequentially.Results Two SNPs in PITX2 genes were rs1051887 and rs28936409,rs1051887:a substitution of cytosine for guanine at nucleotide 954,which suggested the conversion of glutamic acid into glutamine at amino acid residue 106;rs28936409:a substitution of cytosine for guanine at nucleotide 910,which suggested the conversion of arginine into proline at amino acid residue 91.The selected 2 SNPs in the case group and control group showed no polymorphism results.In this research,a new polymorphism 304C ＞ G(Glu102Gln) in PITX2 gene was first identified.Frequencies of CG genetype in case group were higher than control group(x2 =8.531,P ＜0.05),and similar results were found in allelic frequencies(x2 =6.508,P ＜ 0.05).Accordingly,CG genetype increased the risk of interval defect CHD (CG genetype OR =2.833,95 ％ CI:1.297-6.188).Moreover,data showed there was no significant difference in the genotype distribution of SNPs between the case group and control group via Hardy-Weinberg Testing(P ＜ O.05).Conclusions A new SNP 304C ＞ G(Glu102Gln) was found and the CG genetype of the new SNP (304C ＞ G) may increase the risk of interval defect CHD.

Polimorfismos en el gen del transportador de serotonina (SLC6A4) y el trastorno afectivo bipolar en dos centros regionales de salud mental del Eje Cafetero(Colombia) / Polymorphism in the serotonin transporter gene (SLC6A4) and emotional bipolar disorder in two regional mental health centers from the Eje Cafetero (Colombia)

Introducción: Los polimorfismos indel en la región promotora y los polimorfismos de tamaño en el intrón 2 del gen transportador de serotonina se han asociado con el trastorno afectivo bipolar 1 (TAB 1) en diferentes poblaciones. El objetivo fue analizar las frecuencias genotípicas y alélicas en ambas regiones del gen en un estudio de casos y controles en Risaralda y Quindío (Colombia) para encontrar una asociación con TAB 1 y compararlas con estudios similares. Métodos: Se analizaron 133 pacientes y 120 controles. Con PCR se analizaron los polimorfismos indel L y S de la región promotora y los de tamaño (VNTR) STin 2.10 y STin 2.12 del segundo intrón del gen SLC6A4. Resultados: Las frecuencias genotípicas y alélicas en los polimorfismos S y L fueron muy similares en casos y controles. Sin embargo, el genotipo LL se encontró incrementado no significativamente en la población general con TAB 1 (OR=1,89; IC95%= 1,1-3,68) y al separarla por género. Los OR para este genotipo en la oblación general (OR=1,89; IC95%=1,1-3,68) en mujeres (OR=2,22; IC95%=1,04-5,66) y en hombres (OR=1,62; IC95%=0,71-4,39). En los polimorfismos VNTR STin 2.10 y STin2.212 tampoco se observaron diferencias significativas entre las frecuencias genotípicas y alélicas. Conclusiones: No encontramos asociación entre los polimorfismos de las regiones 5-HTTLPR y el intrón 2 del gen transportador de serotonina en los pacientes con TAB 1, ni en la población total, ni al separarla por género. Nuestros resultados son similares a los encontrados en poblaciones caucásicas y difieren de los encontrados en asiáticas y brasileras…

Introduction: The indel polymorphisms in the promoting region and the 2nd intron polymorphisms in the serotonin transporter gene (SLC6A4) have been associated to bipolar disorder 1 (BD1) in several population studies. The objective was to analyze the genotypic and allelic frequencies in both gene regions in a study of cases and controls with individuals from Risaralda and Quindío (Colombia) so as to establish possible associations to BD1, and compare results with previous and similar studies. Methods: 133 patients and 120 controls were studied. L and S indel polymorphisms in the promoting region were analyzed by PCR, together with VNTR STin2.10 and STin 2.12 VNTRs polymorphisms in the 2nd intron of the SLC6A4 gene Results: Genotypic and allelic frequencies for the S and L polymorphisms were similar both in cases and controls. However, the LL genotype was significantly increased both in BD1 population (OR=1.89; CI95%=1.1-3.68), and when discriminated by gender. This particular genotype in general population is OR=2.22; IC95%=1.04-5.66 for women, and OR=1.62; IC 95%=0.71-4.39 for men. No significant genotypic and allelic differences were found for VNTR STin2.10 and STin 2.12. polymorphisms. Conclusions: No association was found between polymorphisms of 5-HTTLPR polymorphisms and the 2nd intron of the serotonin ransporting gene in general patients with BD1, nor when compared by gender. Our results are similar to those reported for Caucasian populations and differ from those of Asian and Brazilian populations…

Germline TP53 mutations and single nucleotide polymorphisms in children / Mutaciones y polimorfismos de un único nucleótido del gen TP53 en línea germinal en niños

Mutations in the gene TP53, which codifies the tumor suppressor protein p53, are found in about 50% of tumors. These mutations can occur not only at somatic level, but also in germline. Pediatric cancer patients, mostly with additional family history of malignancy, should be considered as potential TP53 germline mutation carriers. Germline TP53 mutations and polymorphisms have been widely studied to determine their relation with different tumors' pathogenesis. Our aim was to analyze the occurrence frequency of germline TP53 mutations and polymorphisms and to relate these to tumor development in a pediatric series. Peripheral blood mononuclear cell samples from 26 children with solid tumors [PST] and 21 pediatric healthy donors [HD] were analyzed for germline mutations and polymorphisms in TP53 gene spanning from exon 5 to 8 including introns 5 and 7. These PCR amplified fragments were sequenced to determine variations. A heterozygous mutation at codon 245 was found in 1/26 PST and 0/21 HD. Comparative polymorphisms distribution, at position 14181 and 14201(intron 7), between HD and PST revealed a trend of association (p= 0.07) with cancer risk. HD group disclosed a similar polymorphism distribution as published data for Caucasian and Central/South American populations. This is the first study about TP53 variant frequency and distribution in healthy individuals and cancer patients in Argentina.

El gen que codifica para la proteína supresora de tumor p53 (TP53) se encuentra mutado en aproximadamente el 50% de los tumores. Estas mutaciones pueden presentarse como somáticas o en línea germinal. Los niños con tumores, sobre todo aquellos con historia familiar de enfermedad oncológica, deben considerarse potenciales portadores de mutaciones en línea germinal. Las mutaciones de TP53 y los polimorfismos son estudiados para determinar su relación con la patogénesis de diferentes tumores. El objetivo del trabajo fue analizar la frecuencia de mutaciones y polimorfismos en línea germinal de TP53 y relacionarlos con el desarrollo de tumor en un grupo de pacientes pediátricos. Se analizaron muestras de sangre periférica de 26 pacientes con tumores sólidos [PST] y 21 niños donantes sanos [HD] para determinar la presencia de mutaciones y polimorfismos de TP53 en línea germinal. Se analizó por PCR seguida de secuenciación, la región que comprende a los exones 5 a 8 (incluyendo intrones 5 y 7). En 1/26 PST se encontró una mutación heterocigótica en el codón 245. La distribución de los polimorfismos, en la posición 14181 y 14201 (intrón 7), entre HD y PST mostró una tendencia de asociación (p = 0.07) con el riesgo para desarrollar cáncer. La frecuencia de distribución de dichos polimorfismos en HD fue similar a la publicada para poblaciones caucásicas y de América Central/del Sur. Este estudio aporta información original sobre la frecuencia de distribución de las variantes TP53 en individuos sanos y con tumores en la Argentina.

POPULATION GENETICS OF ONCOMELANIA SPP. IN MAINLAND CHINA(I) RELATIONSHIP BETWEEN SUSCEPTIBILITY AND GENOTYPE FREQUENCY OF SNAILS / 中国血吸虫病防治杂志

The susceptibility of Oncomelania hupensis to Schistosoma japonicum has been shown to be very variable from population to population. This study was undertaken to relate this vari-ation in susceptibility to genetic variability. A total of 33 populations of O. hupensis from sev-eral wide spread localities in mainland China were collected. Snails of all populations were ex-posed in groups to miracidia (20 miracidia per snail) of one laboratory strain of S. japonicum. Infection rate varied from zero to 93. 9%. Population genetic study was carried out by using horizontal starch gel electrophoresis with the 12 specific enzyme systems. A total of 17 genet-ically interpretable loci were observed,7 of these were polymorphic loci. They were Ap,Est -4,Est -5,Got ,Mdh -2,Idh -2 ,Xdh. Allele frequencies were calculated for each population. For logistic regression analysis,susceptibility of the population was scored as 0 when no snail became infected or as 1 when infection rate was more than 0%. Variation in susceptibility was analysed by logistic regression models with genotype frequencies of the 7 polymorphic loci as independent variables. In order to identify the most important factors, both forward and backward stepwise procedures were performed. Results showed that only one variable (genotype frequency of Mdh - 2) entered into the model with a regression coefficient of 13. 706 9 and a constant of -8. 740 9. Results also showed the established model fitted the data well in goodness of fit test,and 93.9% of the populations were correctly classified. It is suggested that a close linkage exists between Mdh-2 gene locus and the susceptibility of O. hupensis.