Unraveling Signatures of Local Adaptation among Indigenous Groups from Mexico.

Few studies have addressed how selective pressures have shaped the genetic structure of the current Native American populations, and they have mostly limited their inferences to admixed Latin American populations. Here, we searched for local adaptation signals, based on integrated haplotype scores and population branch statistics, in 325 Mexican Indigenous individuals with at least 99% Native American ancestry from five previously defined geographical regions. Although each region exhibited its own local adaptation profile, only PPARG and AJAP1, both negative regulators of the Wnt/ß catenin signaling pathway, showed significant adaptation signals in all the tested regions. Several signals were found, mainly in the genes related to the metabolic processes and immune response. A pathway enrichment analysis revealed the overrepresentation of selected genes related to several biological phenotypes/conditions, such as the immune response and metabolic pathways, in agreement with previous studies, suggesting that immunological and metabolic pressures are major drivers of human adaptation. Genes related to the gut microbiome measurements were overrepresented in all the regions, highlighting the importance of studying how humans have coevolved with the microbial communities that colonize them. Our results provide a further explanation of the human evolutionary history in response to environmental pressures in this region.

The genomic landscape of Mexican Indigenous populations brings insights into the peopling of the Americas.

The genetic makeup of Indigenous populations inhabiting Mexico has been strongly influenced by geography and demographic history. Here, we perform a genome-wide analysis of 716 newly genotyped individuals from 60 of the 68 recognized ethnic groups in Mexico. We show that the genetic structure of these populations is strongly influenced by geography, and our demographic reconstructions suggest a decline in the population size of all tested populations in the last 15-30 generations. We find evidence that Aridoamerican and Mesoamerican populations diverged roughly 4-9.9 ka, around the time when sedentary farming started in Mesoamerica. Comparisons with ancient genomes indicate that the Upward Sun River 1 (USR1) individual is an outgroup to Mexican/South American Indigenous populations, whereas Anzick-1 was more closely related to Mesoamerican/South American populations than to those from Aridoamerica, showing an even more complex history of divergence than recognized so far.

GSK3ß Polymorphisms Are Associated with Tumor Site and TNM Stage in Colorectal Cancer.

BACKGROUND: Mutations and polymorphisms of the GSK3ß gene have been associated with several diseases including Alzheimer disease, diabetes and cancer; however, to date, no variants of this gene have been associated with colorectal cancer (CRC). This study aims to explore, for the first time, the association of the GSK3ß rs334558 and rs6438552 polymorphisms with CRC. METHODS: Genomic DNA from 330 CRC patients and healthy blood donors were analyzed. Identification of polymorphisms was made by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. Association was calculated by the odds ratio (OR) test. RESULTS: Patients carrying the C/T genotype for the rs334558 (T>C) polymorphism showed an increased risk for CRC (OR = 1.71, 95% CI: 1.05-2.79, P = 0.039); this association was also observed for TNM stage and tumor location. For the rs6438552 (T>C) polymorphism, the OR analysis showed that patients carrying C/T and C/C genotypes have a decreased risk for CRC (OR = 0.44, 95% CI: 0.27-0.70, P = 0.001 and OR = 0.24, 95% CI: 0.10-0.64, P = 0.001, respectively); this decreased risk was also evident in the stratified analysis by TNM stage and tumor location. Haplotype analysis of these 2 loci of GSK3ß (rs334558 and rs6438552) showed differential distribution. The T-T and C-C haplotype was associated with a decreased risk of CRC, while the T-C haplotype was associated with an increased risk of CRC. CONCLUSION: Our results denote that GSK3ß gene polymorphisms play a significant role in promoting or preventing CRC. Additionally, variations in this gene are associated with the tumor site and the tumor-node-metastasis (TNM) stage in these patients.

Association analysis of calpain 10 gene variants/haplotypes with gestational diabetes mellitus among Mexican women.

Gestational diabetes mellitus (GDM) is a metabolically complex disease with major genetic determinants. GDM has been associated with insulin resistance and dysfunction of pancreatic beta cells, so the GDM candidate genes are those that encode proteins modulating the function and secretion of insulin, such as that for calpain 10 (CAPN10). This study aimed to assess whether single nucleotide polymorphism (SNP)-43, SNP-44, SNP-63, and the indel-19 variant, and specific haplotypes of the CAPN10 gene were associated with gestational diabetes mellitus. We studied 116 patients with gestational diabetes mellitus and 83 women with normal glucose tolerance. Measurements of anthropometric and biochemical parameters were performed. SNP-43, SNP-44, and SNP-63 were identified by polymerase chain reaction (PCR)-restriction fragment length polymorphisms, while the indel-19 variant was detected by TaqMan qPCR assays.  The allele, genotype, and haplotype frequencies of the four variants did not differ significantly between women with gestational diabetes mellitus and controls. However, in women with gestational diabetes mellitus, glucose levels were significantly higher bearing the 3R/3R genotype than in carriers of the 3R/2R genotype of the indel-19 variant (p = 0.006). In conclusion, the 3R/3R genotype of the indel-19 variant of the CAPN-10 gene influenced increased glucose levels in these Mexican women with gestational diabetes mellitus.

Analysis of cytokine gene polymorphisms in Mestizo and native populations from Mexico.

OBJECTIVES: To determine whether the well-known genetic structure of the Mexican population observed with other multiallelic markers can be detected by analyzing functional polymorphisms of cytokine and other inflammatory-response-related genes. METHODS: A total of 834 Mestizo individuals from five Mexican cities and 92 Lacandonians - an Amerindian group from southeastern Mexico - were genotyped for 14 polymorphisms in the CRP, IL10, IL6, TGFB1, TNFA, LTA, ICAM1 IFNG, and IL1RN genes. Allele and haplotype frequencies were used for genetic structure analysis using F-statistics pairwise distances and multidimensional scaling plot. Ancestry analysis was performed, as well. RESULTS: Significant interpopulational differences at the allele and haplotype frequency level were observed, mainly between Northern (Guadalajara, Monterrey, and Culiacan) and Southern (Tierra Blanca and Puebla) Mexican populations. Also, low but significant substructure was detected between some populations from these two broad regions. Interestingly, both Lacandonian populations were highly differentiated from each other and with respect to Mestizos. Consistent with previous data, Amerindian ancestry in the Southern Mexican groups was higher compared to Northern ones. CONCLUSIONS: The Mexican population exhibits regional differences in functional polymorphisms of inflammatory-response genes, as observed for other genetic markers. This information constitutes a reference for epidemiological studies that include these genetic markers to assess the susceptibility of the Mexican population to several immune-response-related diseases, such as diabetes, obesity, and renal disease, which have been shown to be common in the Mexican population but with prevalence differences within this country.

CYP2C9 and CYP2C19 Allele and Haplotype Distributions in Four Mestizo Populations from Western Mexico: An Interethnic Comparative Study.

AIMS: Polymorphisms in the CYP2C9 and CYP2C19 genes confer potential risk for specific adverse drug reactions and therapeutic effect failure. Their frequencies differ among ethnic groups. This study was aimed to describe the distribution of CYP2C9 and CYP2C19 alleles and haplotypes in four Mestizo populations from Western Mexico and their comparison with the reported data from other ethnic groups. METHODS: The CYP2C alleles (CYP2C9*2, CYP2C9*3, CYP2C19*2, and CYP2C19*3) were genotyped using polymerase chain reaction-restriction fragment length polymorphisms analyses using DNA samples from 477 healthy Mestizo individuals of Colima (n = 100), Jalisco (n = 147), Michoacán (n = 117), and Nayarit (n = 113). RESULTS: Frequencies ranged from 2.2-3.0% and 4.8-8.9% for CYP2C9*3 and CYP2C9*2 alleles, respectively, and 5.4-12.0% for CYP2C19*2, whereas the CYP2C19*3 allele was not found. Haplotype GACA, which harbors the loss-of-function allele CYP2C19*2, was the second most frequent (8.7%). Genetic heterogeneity between the Western Mexican populations studied here and the global population was evident (p < 0.05), except for most American populations and other Mexican Mestizo populations. CONCLUSION: Our findings increase the evidence for genetic variability at relevant pharmacogenetic loci and could be useful in association studies involving drugs that are substrates for CYP2C enzymes in the Western Mexican population.

AXIN2 Polymorphisms and Their Association with Colorectal Cancer in Mexican Patients.

AIM: The aim of this study was to investigate the association of the rs2240308 and rs1133683 polymorphisms in the AXIN2 gene with colorectal cancer (CRC) in Mexican patients. MATERIALS AND METHODS: Genomic DNAs from 201 CRC patients and 100 healthy blood donors were analyzed for AXIN2 gene polymorphisms by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. Statistical associations were calculated using the odds ratio (OR) test. RESULTS: The genotype distribution of the rs1133683 polymorphism C > T showed a statistical difference between the two study groups (p = 0.0019). Moreover, OR analyses demonstrated that individuals with either the C/T or T/T genotype have a decreased risk for CRC compared with individuals with the C/C genotype (OR = 0.47, 95% confidence interval [CI] = 0.25-0.86, p = 0.0134 and OR = 0.24, 95% CI = 0.10-0.57, p = 0.005, respectively). This association was also evident in a stratified analysis based on tumor-node-metastasis (TNM) stage. For the rs2240308 polymorphism C > T, the OR analysis showed a significantly increased risk for carriers of the T/T genotype (OR = 2.64, 95% CI = 1.12-6.24, p = 0.0236) and this association was also evident in the stratified analysis by TNM stage. CONCLUSION: Our results indicate the possibility that variations in the AXIN2 gene may play a significant role in promoting or preventing CRC development.

[Association analysis of SNP-63 and indel-19 variant in the calpain-10 gene with polycystic ovary syndrome in women of reproductive age]. / Análisis de asociación del SNP-63 y la variante indel-19 del gen de calpaína-10 con síndrome de ovario poliquístico en mujeres en edad reproductiva.

BACKGROUND: Polycystic ovary syndrome is a complex and heterogeneous disease involving both reproductive and metabolic problems. It has been suggested a genetic predisposition in the etiology of this syndrome. The identification of calpain-10 gene (CAPN10) as the first candidate gene for type 2 diabetes mellitus, has focused the interest in investigating their possible relation with the polycystic ovary syndrome, because this syndrome is associated with hyperinsulinemia and insulin resistance, two metabolic abnormalities associated with type 2 diabetes mellitus. OBJECTIVE: To investigate if there is association between the SNP-63 and the variant indel-19 of the CAPN10 gene and polycystic ovary syndrome in women of reproductive age. MATERIAL AND METHODS: This study included 101 women (55 with polycystic ovary syndrome and 46 without polycystic ovary syndrome). The genetic variant indel-19 was identified by electrophoresis of the amplified fragments by PCR, and the SNP-63 by PCR-RFLP. RESULTS: The allele and genotype frequencies of the two variants do not differ significatly between women with polycystic ovary syndrome and control women group. The haplotype 21 (defined by the insertion allele of indel-19 variant and C allele of SNP-63) was found with higher frequency in both study groups, being more frequent in the polycystic ovary syndrome patients group, however, this difference was not statistically significant (p = 0.8353). CONCLUSIONS: The results suggest that SNP-63 and indel-19 variant of the CAPN10 gene do not represent a risk factor for polycystic ovary syndrome in our patients group.

Adiposidade corporal, mas não resistência insulínica, associa-se ao polimorfismo -675 4G/5G no gene PAI-1 em uma amostra de crianças mexicanas / Body adiposity but not insulin resistance is associated with -675 4G/5G polymorphism in the PAI-1 gene in a sample of Mexican children

OBJETIVO: Elaboramos este estudo para avaliar se o polimorfismo -675 4G/5G no gene inibidor 1 do ativador do plasminogênio se associa à obesidade e à resistência insulínica em crianças mexicanas. MÉTODOS: Foi realizado um estudo transversal em 174 crianças, 89 delas com peso normal e 85 obesas, variando sua idade de 6 a 13 anos. Todas as crianças eram do estado de Guerrero e foram recrutadas de três escolas primárias na cidade de Chilpancingo, México. Os níveis de insulina foram determinados por prova imunoenzimática. Foi usado o modelo de avaliação da homeostase para determinar resistência insulínica. O polimorfismo -675 4G/5G no gene PAI-1 foi analisado pelo método reação de polimerase em cadeia-polimorfismo no comprimento dos fragmentos de restrição. RESULTADOS: A prevalência de resistência insulínica no grupo obeso foi mais alta (49,41%) do que no grupo com peso normal (16,85%). O polimorfismo 4G/5G do PAI-1 foi encontrado em equilíbrio de Hardy Weinberg. O genótipo 4G/5G contribuiu para um aumento significativo da relação cintura-quadril (β = 0,02, p = 0,006), da circunferência da cintura (β = 4,42, p = 0,009) e da espessura da prega subescapular (β = 1,79, p = 0,04), mas não se relacionou com a resistência insulínica. CONCLUSÃO: O genótipo -675 4G/5G do gene PAI-1 se associou a aumento da adiposidade corporal em crianças mexicanas.

OBJECTIVE: To assess whether the -675 4G/5G polymorphism in the plasminogen activator inhibitor-1 gene is associated with obesity and insulin resistance in Mexican children. METHODS: A cross-sectional study was performed in 174 children, 89 with normal-weight and 85 with obesity, aged from 6 to 13 years. All children were from state of Guerrero, and recruited from three primary schools in the city of Chilpancingo, Mexico. Insulin levels were determined by immunoenzymatic assay. The homeostasis model assessment was used to determine insulin resistance. The -675 4G/5G polymorphism in PAI-1 gene was analyzed by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: The prevalence of insulin resistance in the obese group was higher (49.41%) than in the normal-weight group (16.85%). The 4G/5G PAI-1 polymorphism was found in Hardy Weinberg equilibrium. The 4G/5G genotype contributed to a significant increase in waist-hip ratio (β = 0.02, p = 0.006), waist circumference (β = 4.42, p = 0.009), and subscapular skinfold thickness (β = 1.79, p = 0.04); however, it was not related with insulin resistance. CONCLUSION: The -675 4G/5G genotype of PAI-1 gene was associated with increase of body adiposity in Mexican children.

Low prevalence of interleukin-6 haplotypes associated with a decreased risk of type 2 diabetes in Mexican subjects with a family history of type 2 diabetes.

BACKGROUND AND AIMS: There is evidence that family history of type 2 diabetes (FHT2D) and single nucleotide polymorphisms (SNP) on the IL-6 gene promoter region are separately associated with the risk of developing type 2 diabetes. However the relationship between adult Mexican subjects with FHT2D and genotypes/haplotypes for IL-6 gene has not been explored. The aim of the present work was to study the prevalence of IL-6 -598G>A-572G>C-174G>C haplotypes among subjects with FHT2D and to determine whether their presence influences the relationship between FHT2D and risk factors for diabetes. METHODS: Two hundred fifty eight nondiabetic subjects participated in this study; 153 with and 105 without FHT2D. Polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) was used for genotyping. Logistic regression analysis was employed to assess the impact of IL-6 haplotypes on FHT2D per se and hyperinsulinemia and insulin resistance as risk factors for diabetes. RESULTS: Subjects with FHT2D showed a higher prevalence of hyperinsulinemia and insulin resistance (IR) than those without FHT2D (14.4 vs. 5.7%, p = 0.029, and 14.2 vs. 7.0% p = 0.050, respectively). Lower prevalence of -598 -572-174 (AGC)-haplotype (19%) in subjects with FHT2D was observed as well as a lower prevalence of hyperinsulinemia and IR among AGC haplotype carriers (12 and 14%, respectively). The relationship between FHT2D and IR was modified by the presence of AGC haplotype (from OR, 2.70; 95% CI, 0.99-7.36; p = 0.050 OR, 30.08; 95% CI, 0.58-1,568.06; p = 0.092). CONCLUSIONS: IL-6 -598/-572/-174 (AGC) haplotype has a low prevalence among first-degree relatives of subjects with type 2 diabetes. Our results suggest that this haplotype is associated with decreased risk of type 2 diabetes in Mexican subjects with FHT2D.

Body adiposity but not insulin resistance is associated with -675 4G/5G polymorphism in the PAI-1 gene in a sample of Mexican children.

OBJECTIVE: To assess whether the -675 4G/5G polymorphism in the plasminogen activator inhibitor-1 gene is associated with obesity and insulin resistance in Mexican children. METHODS: A cross-sectional study was performed in 174 children, 89 with normal-weight and 85 with obesity, aged from 6 to 13 years. All children were from state of Guerrero, and recruited from three primary schools in the city of Chilpancingo, state of Guerrero, Mexico. Insulin levels were determined by immunoenzymatic assay. The homeostasis model assessment was used to determine insulin resistance. The -675 4G/5G polymorphism in PAI-1 gene was analyzed by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: The prevalence of insulin resistance in the obese group was higher (49.41%) than in the normal-weight group (16.85%). The 4G/5G PAI-1 polymorphism was found in Hardy Weinberg equilibrium. The 4G/5G genotype contributed to a significant increase in waist-hip ratio (ß=0.02, p=0.006), waist circumference (ß=4.42, p=0.009), and subscapular skinfold thickness (ß=1.79, p=0.04); however, it was not related with insulin resistance. CONCLUSION: The -675 4G/5G genotype of PAI-1 gene was associated with increase of body adiposity in Mexican children.

[Pharmacogenetics and antiepileptic drug metabolism: implication of genetic variants in cytochromes P450]. / Farmacogenetica y metabolismo de farmacos antiepilepticos: implicacion de variantes geneticas en citocromos P450.

INTRODUCTION: Antiepileptic drugs (AEDs) are used for the seizures control in patients with epilepsy, however 20-30% of epileptic patients are drug resistant. Several factors contributing to the variability of the AEDs response, and this variability can be partially attributed to the presence of sequence variations (polymorphisms) in genes encoding enzymes involved in the AEDs metabolism. AIM: To describe the polymorphisms in genes that encoding for proteins involved in the metabolism of some of the major AEDs, focusing on enzymes cytochrome P450 (CYP450). DEVELOPMENT: There are some polymorphisms in genes encoding proteins involved in drug metabolism, particularly enzymes of superfamily CYP450, that are already considered of clinical utility in the therapeutic management. These genetic variants contribute to the variability of the activity of metabolizing enzymes, which in turn influencing the poor or inadequate therapeutic response, as well as in the occurrence of adverse effects. CONCLUSIONS: The identification of interindividual variability in the response to AEDs may allow the personalized treatment with the aim of maximize the efficiency and minimize risk, regardless of the clinical variability and adverse effects could be manifest in a minority of the patients.

TITLE: Farmacogenetica y metabolismo de farmacos antiepilepticos: implicacion de variantes geneticas en citocromos P450.Introduccion. Los farmacos antiepilepticos (FAE) son la base para el control de las crisis en pacientes con epilepsia; sin embargo, se conoce que el 20-30% de los pacientes son farmacorresistentes. Son diversos los factores que contribuyen a la variabilidad de la respuesta a los FAE, y esta variabilidad puede atribuirse, al menos en parte, a la presencia de polimorfismos (variaciones de la secuencia) en genes que codifican para enzimas involucradas en el metabolismo de los FAE. Objetivo. Describir las variaciones de la secuencia en genes que codifican para proteinas implicadas en el metabolismo de algunos de los principales FAE, con enfasis en las enzimas citocromo P450 (CYP450). Desarrollo. Existen algunos polimorfismos en genes que codifican para proteinas involucradas en el metabolismo de farmacos, particularmente enzimas de la superfamilia CYP450, que se consideran ya de utilidad clinica en el manejo terapeutico. La presencia de estas variantes geneticas contribuye a la variabilidad de la actividad de enzimas metabolizadoras, lo que, a su vez, influye en la pobre o inadecuada respuesta terapeutica, e incluso en la aparicion de efectos adversos. Conclusiones. La identificacion de la variabilidad interindividual en la respuesta a los diversos FAE puede permitir la individualizacion del tratamiento con la intencion de maximizar su eficacia y minimizar el riesgo, independientemente de que la variabilidad clinica y los efectos adversos se presenten en una minoria de pacientes.

Association analysis between -308G/A and -238G/A TNF-alpha gene promoter polymorphisms and insulin resistance in Mexican women with gestational diabetes mellitus.

BACKGROUND: Gestational diabetes mellitus (GDM) is characterized by insulin resistance. It has been described that tumor necrosis factor α (TNF-α) plays a key role in the pathogenesis of insulin resistance; moreover, increased levels of this proinflammatory cytokine have been reported in women with GDM. Therefore, this study was aimed to assess the presence of associations between the -308G/A and -238G/A polymorphisms and specific haplotypes of the TNF-α gene promoter region and insulin resistance in Mexican women with GDM. METHODS: This study included 51 women with GDM and 44 pregnant women with normal glucose tolerance. Measurements of anthropometric parameters and biochemical estimations were performed. We genotyped the TNF-α -308G/A and -238G/A polymorphisms using polymerase chain reaction-restriction fragment length polymorphism analysis. RESULTS: The genotype and allele frequencies of both polymorphisms did not differ significantly between the women with GDM and the controls. However, we found that the frequency of the AG haplotype was significantly increased in the patients with GDM compared with controls (P = 0.019; odds ratio, 4.11; 95% confidence interval, 1.31-12.85). In patients with GDM, we observed that insulin levels and homeostasis model assessment of insulin resistance were significantly higher in women bearing the G/G genotype than in carriers of the G/A and A/A genotypes of the -308G/A polymorphism (P = 0.022 and P = 0.043, respectively). CONCLUSIONS: Our results suggest that the G/G genotype of the TNF-α -308G/A polymorphism increases insulin levels and insulin resistance in women with GDM and that the AG haplotype is a genetic risk factor for GDM in our study population.

Tumor necrosis factor-alpha gene promoter -308G/A and -238G/A polymorphisms in Mexican patients with type 2 diabetes mellitus.

The association between some Tumor necrosis factor-alpha (TNF-α) promoter polymorphisms and Type 2 diabetes mellitus (T2DM) remains controversial. Ethnic differences may play a role in these conflicting results. The aim of this study was to investigate the association between -308G/A and -238G/A polymorphisms located in the promoter region of the TNF-α gene and T2DM in Mexican mestizo patients. Nine hundred four individuals (259 patients with T2DM and 645~controls) were genotyped for the -308G/A and -238G/A polymorphisms by PCR--RFLP. We found that the -238A allele increased the risk of developing T2DM in Mexican patients (OR=1.57, 95% CI: 1.07-2.29; p=0.018). Moreover, we found that the frequency of the GA haplotype (created by the -308G and -238A alleles) was significantly increased in patients with T2DM when compared with controls (OR =1.56, 95% CI: 1.05-2.31; p=0.026). Our results suggest that the -238G/A polymorphism and a specific haplotype (GA) are genetic risk factors for the development of T2DM in Mexican population.

Influence of CRP, IL6, and TNFA gene polymorphisms on circulating levels of C-reactive protein in Mexican adolescents.

BACKGROUND AND AIMS: Obesity correlates with a chronic and low-grade inflammation status. C-reactive protein (CRP) measurement has been used as an independent risk marker for future cardiovascular events. CRP level shows interindividual variability due to environmental and genetic factors. The aim of this study was to assess the association of functional polymorphisms on CRP, IL6, and TNFA genes with serum CRP levels in Mexican mestizo adolescents. METHODS: Body mass index (BMI), serum high-sensitivity C-reactive protein (hsCRP) levels, and genotypes for CRP+1444C>T, IL6-174G>C, and TNFA-308G>A polymorphisms were obtained from 418 unrelated Mexican adolescents. Genetic association with hsCRP levels was evaluated by means of a dominant genetic model with uni- and multivariate analysis. RESULTS: Genotype frequencies for all three polymorphisms were according to Hardy-Weinberg equilibrium (HWE). CRP+1444T, TNFA-308A, and IL6-174C allele frequencies were 37, 7, and 10%, respectively. CRP+1444T was associated with higher mean CRP levels independent of age, gender and BMI (ß = 0.21; 95% confidence interval [95% CI] = 0.02-0.39); p = 0.030). IL6-174C was associated with low CRP levels in the overweight group (p = 0.005). IL6-174G>C and TNFA-308G>A allele frequencies observed from this Mexican sample were similar to data for other Mexican populations. CONCLUSIONS: The CRP+1444C>T polymorphism was associated with CRP levels in Mexican adolescents and could be used as a genetic marker for the early detection of individuals at risk for developing obesity-related conditions such as cardiovascular disease or type 2 diabetes mellitus in early adulthood.

Analysis of the association of preeclampsia with polymorphisms of the INS, INSR and IRS1 genes in Mexican women.

BACKGROUND/AIMS: It has been proposed that preeclampsia is a metabolic syndrome of pregnancy. The polymorphisms PstI and MaeIII of INS, NsiI of INSR and Ala513Pro and Gly972Arg of IRS1 have been associated with metabolic syndrome; moreover, the products of these genes are functionally contiguous during insulin signaling. The aim of this study was to assess whether these polymorphisms are associated with preeclampsia. METHODS: 46 normotensive pregnant women and 43 preeclamptic patients were included in the study to develop a clinical, biochemical and genotypic profile of preeclampsia. Clinical evaluation consisted of measurement of blood pressure, height and weight. Peripheral blood samples were collected for determination of fasting glucose and insulin concentrations and for extraction of genomic DNA. Proteinuria was determined. Polymorphisms were detected using PCR-RFLP. RESULTS: The normotensive and preeclampsia groups did not differ significantly in clinical and biochemical traits, except for systolic and diastolic blood pressure (p < 0.0001). Polymorphisms previously associated with metabolic syndrome in Mexican populations were not associated with preeclampsia in Mexican women (p > 0.05). CONCLUSION: The lack of an association between preeclampsia and the polymorphisms studied suggests that other genes whose products do not have direct functional interaction with metabolic syndrome or epigenetic factors may play a role in preeclampsia.

Mucopolisacaridosis tipo I, III y VI: actividad enzimática y determinación cualitativa y cuantitativa de glucosaminoglucanos urinarios / Mucopolysaccharidoses types I, III and VI: enzimatic activity quantitative and qualiatative determination of urinary glycosaminoglycans

Introducción. Las mucopolisacaridosis (MPS) son un grupo heterogéneo de enfermedades hereditarias, originadas por la deficiencia de enzimas lisosomales que catalizan la degradación de los glucosaminoglucanos (GAGs). Actualmente se conocen 11 deficiencias enzimáticas que originan 8 fenotipos distintos y expresan una variedad de síntomas clínicos. Material y métodos. Doce pacientes con diagnóstico clínico de MPS (4 con MPS I, 2 con MPS IIIB y 6 con MPS VI) dos fueron estudiados bioquímicamente mediante la cuantificación de GAGs urinarios, su identificación a través de electroforesis en acetato de celulosa y la correlación con la actividad enzimática en leucocitos. Resultados. En todos los casos la concentración de GAGs/creatinina estuvo elevada en comparación con un grupo control. La electroforesis reveló la presencia de los GAGs esperados en cada tipo de MPS y la actividad enzimática fue deficiente en los 12 pacientes estudiados. Conclusiones. La aplicación de los métodos anteriores en pacientes con MPS, es una poderosa herramienta a utilizar como diagnóstico.

Deteccion de Mycobacterium tuberculosis mediante la reaccion en cadena de la polimerasa en una poblacion seleccionada del noroccidente de Mexico / Detection of Mycobacterium tuberculosis with polymerase chain reaction in a selected population in northwestern Mexico

Este estudio compara la detección de Mycobacterium tuberculosis mediante baciloscopia (tinción de Ziehl-Neelsen), cultivo en medio de L"wenstein-Jensen y reacción en cadena de la polimerasa (RCP) realizada con ADN extraído directamente de distintos tipos de muestras. Se analizaron 252 muestras (114 de esputo, 96 de orina, 15 de LCR y 27 de otros tipos) de 160 pacientes con sospecha de tuberculosis en cualquiera de sus formas que acudieron al Laboratorio de Patología Clínica del Hospital de Especialidades del Centro Médico Nacional de Occidente del Instituto Mexicano del Seguro Social. En todos los casos se realizó tinción de Ziehl-Neelsen, cultivo en medio de L"wenstein-Jensen y amplificación por RCP de un segmento de 285 pares de bases específico del complejo M. tuberculosis. De las 252 muestras, 18 fueron positivas para micobacterias no tuberculosas en el cultivo. De las 234 restantes, 12 (5,1 por ciento) fueron positivas en la RCP y el cultivo, 174 (74,4 por ciento) negativas en ambas pruebas, 47 (20,1 por ciento) positivas en la RCP y negativas en el cultivo y 1 (0,4 por ciento) negativa en la RCP y positiva en el cultivo; tomando el cultivo como prueba de referencia, la RCP proporcionó una sensibilidad de 92,3 por ciento, una especificidad de 78,7 por ciento, un valor predictivo positivo de 20,3 por ciento y un valor predictivo negativo de 99,4 por ciento. El límite de detección de la RCP en ADN extraído de cultivo fue de 10 fg (equivalente a 4 o 5 micobacterias). También en comparación con el cultivo, la RCP identificó correctamente a la totalidad de las micobacterias del complejo M. tuberculosis. Tomando como prueba de referencia el cultivo, al analizar únicamente las muestras de esputo, la RCP directa proporcionó una sensibilidad de 90,9 por ciento, una especificidad de 89,5 por ciento, un valor predictivo positivo de 52,6 por ciento y un valor predictivo negativo de 98,7 por ciento. La RCP es una técnica sensible y específica para detectar el complejo M. tuberculosis en muestras tanto positivas como negativas en la baciloscopia. Un procedimiento controlado de RCP permite establecer o excluir el diagnóstico de tuberculosis en un tiempo que se reduce de m s de tres semanas a tan solo 24 a 48 horas, lo cual resulta particularmente útil cuando es necesario un diagnóstico temprano para establecer el pronóstico del paciente o en casos de transplante de órganos

This study compares the detection of Mycobacterium tuberculosis through bacilloscopy (Ziehl-Neelsen stain), growth in Lowenstein-Jensen medium, and polymerase chain reaction (PCR) carried out with DNA taken directly from various types of samples. A total of 252 samples were analyzed (114 sputum, 96 urine, 15 cerebrospinal fluid, and 27 of other types) from 160 patients with any form of suspected tuberculosis who came to the Clinical Pathology Laboratory of the Specialties Hospital of the Western National Medical Center of the Mexican Social Security Institute. In all cases ZiehlNeelsen stains were done, as were also cultures with Lowenstein-Jensen medium and PCR amplification of a segment of 285 base pairs specific to the M. tuberculosis complex. Of the 252 samples, with the culture, 18 were positive for nontuberculous mycobacteria. Of the 234 others, 12 (5.1%) were positive with the PCR and the culture, 174 (74.4%) negative in both tests, 47 (20.1%) positive with the PCR and negative with the culture, and 1 (0.4%) negative with the PCR and positive with the culture. Using the culture as the reference test, the PCR provided a sensitivity of 92.3%, a specificity of 78.7%, a positive predictive value of 20.3%, and a negative predictive value of 99.4%. The PCR detection limit with DNA taken from culture was 10 fg, equivalent to four or five mycobacteria. Also in comparison with the culture, the PCR correctly identified the totality of the mycobacteria of the M. tuberculosis complex. Taking the culture as the reference test, when analyzing just the sputum samples, the direct PCR provided a sensitivity of 90.9%, a specificity of 89.5%, a positive predictive value of 52.6%, and a negative predictive value of 98.7%. The PCR is a sensitive and specific technique for detecting the M. tuberculosis complex in both positive and negative bacilloscopy samples. A controlled PCR procedure makes it possible to establish or to exclude the diagnosis of tuberculosis in a time that is reduced from more than three weeks to just 24 to 48 hours. This is particularly useful when an early diagnosis is needed to establish a patient's prognosis or in organ transplant cases.

Mucopolysaccharidoses type II: Enzymatic activity and quantitative and qualitative studies of urinary glycosaminoglycans in five patients

Five patients presenting Hunter's syndrome were biochemically studied. Quantification of urinary glycosaminoglycans (GAGs), electrophoretic characterizatio and correlation with ensymatic activity in leucocytes were carried out. In all cases, urinary GAGs/creatinine ratio was increased. Electrophoresis revealed the presence of heparan sulfate (HS) and dermatan sulfate (DS) in four cases (80 perecent), but in the remaining patient, only DS was present. In all patients, deficient enzymatic activity was demonstrated. These results show evidences of biochemical differences in thys syndrome