Association of a serotonin transporter gene (SLC6A4) 5-HTTLPR polymorphism with body mass index categories but not type 2 diabetes mellitus in Mexicans

The serotonergic system has been hypothesized to contribute to the biological susceptibility to type 2 diabetes mellitus (T2DM) and body-mass index (BMI) categories. We investigate a possible association of 5-HTTLPR polymorphism (L and S alleles) in the promoter region of the serotonin transporter gene (SLC6A4) with the development of T2DM and/or higher BMI by analyzing a sample of 138 individuals diagnosed with T2DM and 172 unrelated controls from the Mexican general population. In the total sample genotypes were distributed according to Hardy-Weinberg equilibrium, and S allele frequency was 0.58. There was no statistical association between 5-HTTLPR polymorphism and the development of T2DM in this Mexican population sample (p = 0.12). Nevertheless, logistic regression analysis of the L allele and increased BMI disclosed an association, after adjusting for age, sex and T2DM (p = 0.02, OR 1.74, 95% CI: 1.079-2.808)

Association of the 5HTTLPR Polymorphism with Obesity in Mexican Women with High Native American Ancestry

Aims: The 5HTT gene has been associated with obesity; this study aimed to determine the association between L- and S-alleles at the 5HTTLPR polymorphism with obesity in indigenous Mexican populations. Materials and Methods: A total of 362 individuals, 289 belonging to eight Native American (NA) groups; 40 Mexican mestizos; and 33 Caucasian Mennonites were enrolled in a cross-sectional study. High (≥90%) and low (30 kg/m2 was considered as obese. The L- and S-alleles of the 5HTTLPR locus were identified by PCR; the association between alleles and obesity was performed by logistic regression analysis. Results: A significantly lower prevalence of obesity (35%) was observed in participants from communities with high NA ancestry (p < 0.005). Under a dominant heritance model the L-allele was associated with obesity in women with high NA ancestry (odds ratio [OR] 7.27; 95% confidence interval [CI] 1.6–32.5; p = 0.009) but not in women with low NA ancestry (OR 0.83; 95% CI 0.3–2.2; p = 0.71); no association was observed in men. Conclusion:Our results suggest that the 5HTTLPR L-allele is a risk factor for developing obesity in Mexican women with high NA ancestry (≥90%)

Amplified Genes May Be Overexpressed, Unchanged, or Downregulated in Cervical Cancer Cell Lines

Several copy number-altered regions (CNAs) have been identified in the genome of cervical cancer, notably, amplifications of 3q and 5p. However, the contribution of copy-number alterations to cervical carcinogenesis is unresolved because genome-wide there exists a lack of correlation between copy-number alterations and gene expression. In this study, we investigated whether CNAs in the cell lines CaLo, CaSki, HeLa, and SiHa were associated with changes in gene expression. On average, 19.2% of the cell-line genomes had CNAs. However, only 2.4% comprised minimal recurrent regions (MRRs) common to all the cell lines. Whereas 3q had limited common gains (13%), 5p was entirely duplicated recurrently. Genome-wide, only 15.6% of genes located in CNAs changed gene expression; in contrast, the rate in MRRs was up to 3 times this. Chr 5p was confirmed entirely amplified by FISH; however, maximum 33.5% of the explored genes in 5p were deregulated. In 3q, this rate was 13.4%. Even in 3q26, which had 5 MRRs and 38.7% recurrently gained SNPs, the rate was only 15.1%. Interestingly, up to 19% of deregulated genes in 5p and 73% in 3q26 were downregulated, suggesting additional factors were involved in gene repression. The deregulated genes in 3q and 5p occurred in clusters, suggesting local chromatin factors may also influence gene expression. In regions amplified discontinuously, downregulated genes increased steadily as the number of amplified SNPs increased (p<0.01, Spearman's correlation). Therefore, partial gene amplification may function in silencing gene expression. Additional genes in 1q, 3q and 5p could be involved in cervical carcinogenesis, specifically in apoptosis. These include PARP1 in 1q, TNFSF10 and ECT2 in 3q and CLPTM1L, AHRR, PDCD6, and DAP in 5p. Overall, gene expression and copy-number profiles reveal factors other than gene dosage, like epigenetic or chromatin domains, may influence gene expression within the entirely amplified genome segments

MDR1 C3435T Polymorphism in Mexican Children with Acute Lymphoblastic Leukemia and in Healthy Individuals

To determine the influence of the MDR1 C3435T polymorphism on the development of childhood acute lymphoblastic leukemia (ALL), we studied 107 children with ALL and 111 healthy subjects. All subjects were genotyped for the C3435T polymorphism using the polymerase chain reaction–restriction fragment length polymorphism method. The genotype frequencies in the patients were 17% homozygous CC, 61% heterozygous CT, and 22% homozygous TT; in healthy individuals the genotype frequencies were 14% CC, 53% CT, and 33% TT. In patients with ALL the allele frequencies were 0.47 for the C allele and 0.53 for the T allele; in the healthy group these allele frequencies were 0.40 and 0.60 for the C and T alleles, respectively. No significant differences in allele frequency (p \u3e 0.176) and genotype frequency (p \u3e 0.255) were detected between the two groups. These findings suggest that the CT or TT genotype does not increase the risk for childhood ALL in Mexican patients. On the other hand, significant differences in allele frequencies were detected in the comparison of Mexican healthy subjects with other populations. Whether these differences are fortuitous or related to diverse genetic backgrounds remains to be elucidated

XRCC1 R194W and R399Q Polymorphisms and Colorectal Cancer Risk in a Northeastern Mexican Population

Colorectal cancer (CRC) is one of the most common cancers worldwide. Its etiopathogenesis is complex, mainly influenced by genetic instability caused by the accumulation of mutations. The XRCC1 gene, which is involved in DNA repair, has been associated with CRC through the R194W (C194T) and R399Q (G399A) polymorphisms, but the results are inconsistent. Here, we analyzed the association of these polymorphisms with sporadic CRC in a northeastern Mexican population, including 155 male CRC patients and 155 male controls. Genotyping was performed using the RFLP method. An association with CRC was found for the 399A allele (G vs A; OR = 1.48 (1.03–2.13), P=0.034) and for the 399AA genotype in a codominant model (AA vs GG; OR = 3.11 (1.06–9.10), P=0.031). In contrast, there were no significant differences between CRC patients and controls for the C194T polymorphism (C vs T; OR = 0.82 (0.52–1.31), P=0.41). These results are consistent with many similar studies, but further research is needed to verify whether the XRCC1 R194W and R399Q polymorphisms play a role in CRC etiology. The functional significance of these polymorphisms is unclear, but some studies suggest that they influence DNA repair capacity and, thus, cancer risk

TYMS 2R3R polymorphism and DPYD [IVS]14+1G>A gene mutation in Mexican colorectal cancer patients

Objective: To examine the association between TYMS 2R3R polymorphism and DPYD [IVS]14+1G>A mutation by comparing healthy subjects with colorectal cancer (CRC) patients in the Mexican population. Method: Genotyping of the 2R/3R was performed by polymerase chain reaction (PCR) and [IVS]14+1G>A mutation by real-time PCR analysis. Results: The observed frequencies of the TYMS 2R3R polymorphism and the -[IVS]14+1G>A mutation in DPYD did not indicate an increased risk for CRC (p>0.05). However we observed an association of the 2R/2R (OR 3.08, 95% CI 1.66-6.08, p=0.0017) and heterozygous (OR 1.98, 95% CI 1.32-2.97, p=0.0012) genotypes as risk factors when comparing controls and CRC patients that were also tobacco consumers. An association between the genotype and the disease was evident. The distribution of the 2R/2R genotype and hematological toxicity (adjusted OR 2.26, 95% CI 1.54-4.45, p=0.0259), heterozygous (2R/3R) with tumor stage III-IV (OR 1.81, 95% CI 1.11-2.94, p=0.020) and 2R/2R-2R/3R in non-chemotherapy response CRC patients with hematological (OR 2.3, 95% CI 1.21-4.4, p=0.014) and gastric toxicities (OR 3.11, 95% CI 1.18-8.2, p=0.035) confirmed that this factor may significantly contribute to the CRC susceptibility. Conclusion: TYMS 2R3R polymorphism and the -[IVS]14+1G>A mutation in DPYD was not associated with susceptibility to CRC. However, the 2R/2R and 2R/3R genotypes of TYMS polymorphism could significantly contribute to hematological and gastric toxicity in CRC patients in this sample population

Rescue Mechanical Thrombectomy After Failed Thrombolysis in a Pregnant Patient Case Report

Pulmonary thromboembolism in pregnancy is a complication that directly impacts morbidity and mortality, the incidence is conditioned by the prothrombotic state during pregnancy and in the postpartum period, since the most important risk factor in this context is deep vein thrombosis, a condition that exponentially increases the risk of presenting thrombotic events such as pulmonary thromboembolism, in the clinical presentation there are no differences in this context, however it is important to note that to date there are no risk scales where pregnancy is included as part of the factors within a scale, so clinical diagnosis, biochemical and imaging is of vital importance, in order to reduce the potential complications and outcome of this group of patients. In the diagnostic approach, image diagnosis such as the Transthoracic/Tranesophageal Echocardiogram is of vital importance, with the purpose of searching for etiology. It is worth mentioning that in the group of patients in whom thrombotic events of the ischemic CVD type are evident, within the diagnostic possibilities are atherosclerosis of large vessels, cardioembolism or vasculitis, in turn in the group of patients in whom evidence of thrombotic events such as PE must be ruled out the possibility of structural alterations at the level of right cavities, as well as shunts such as foramen. Patent oval, ASD, once identified, there are various Echocardiographic techniques for the detection of these conditions, such as echocardiogram with air-fluid contrast, through which morphological characteristics are visualized, being important for the assessment of direct risk, in the event of possible complications. short-medium term, such as the risk of presenting cerebrovascular events, is of vital importance when making therapeutic decisions, since once the risk is identified, surgical/percutaneous therapeutic options are available, according to the patient's context. In the present case, reference is made to a young patient whose main risk factor is Pregnancy 10.5 SDG, and whose initial presentation to the case was pulmonary thromboembolism of main branches, secondary to deep vein thrombosis, in which thrombolysis was performed with rtPA, continuing with data of hemodynamic instability for which invasive treatment was decided by mechanical thrombectomy with an immediate favorable response, in turn presented a second thrombotic event, of the Ischemic cerebrovascular event type in the territory corresponding to the posterior cerebral artery secondary to a patent foramen ovale. with a favorable outcome after timely multidisciplinary treatmen