Association of CYP3A4-392A/G, CYP3A5-6986A/G, and ABCB1-3435C/T Polymorphisms with Tacrolimus Dose, Serum Concentration, and Biochemical Parameters in Mexican Patients with Kidney Transplant.

Tacrolimus (TAC) is an immunosuppressant drug that prevents organ rejection after transplantation. This drug is transported from cells via P-glycoprotein (ABCB1) and is a metabolic substrate for cytochrome P450 (CYP) 3A enzymes, particularly CYP3A4 and CYP3A5. Several single-nucleotide polymorphisms (SNPs) have been identified in the genes encoding CYP3A4, CYP3A5, and ABCB1, including CYP3A4-392A/G (rs2740574), CYP3A5 6986A/G (rs776746), and ABCB1 3435C/T (rs1045642). This study aims to evaluate the association among CYP3A4-392A/G, CYP3A5-6986A/G, and ABCB1-3435C/T polymorphisms and TAC, serum concentration, and biochemical parameters that may affect TAC pharmacokinetics in Mexican kidney transplant (KT) patients. METHODS: Forty-six kidney transplant recipients (KTR) receiving immunosuppressive treatment with TAC in different combinations were included. CYP3A4, CYP3A5, and ABCB1 gene polymorphisms were genotyped using qPCR TaqMan. Serum TAC concentration (as measured) and intervening variables were assessed. Logistic regression analyses were performed at baseline and after one month to assess the extent of the association between the polymorphisms, intervening variables, and TAC concentration. RESULTS: The GG genotype of CYP3A5-6986 A/G polymorphism is associated with TAC pharmacokinetic variability OR 4.35 (95%CI: 1.13-21.9; p = 0.0458) at one month of evolution; in multivariate logistic regression, CYP3A5-6986GG genotype OR 9.32 (95%CI: 1.54-93.08; p = 0.028) and the use of medications or drugs that increase serum TAC concentration OR 9.52 (95%CI: 1.79-88.23; p = 0.018) were strongly associated with TAC pharmacokinetic variability. CONCLUSION: The findings of this study of the Mexican population showed that CYP3A5-6986 A/G GG genotype is associated with a four-fold increase in the likelihood of encountering a TAC concentration of more than 15 ng/dL. The co-occurrence of the CYP3A5-6986GG genotype and the use of drugs that increase TAC concentration correlates with a nine-fold increased risk of experiencing a TAC at a level above 15 ng/mL. Therefore, these patients have an increased susceptibility to TAC-associated toxicity.

Association of the rs1126616 and rs9138 Variants in the SPP1 Gene among Mexican Patients with Systemic Lupus Erythematosus and Lupus Nephritis.

Systemic lupus erythematosus (SLE) is a multisystem disease considered a prototype of the main autoimmune disease and presents serious complications, such as lupus nephritis (LN), which generates a significant impact on morbidity and mortality. The SPP1 gene encodes the osteopontin (OPN) protein, which plays a crucial role in the regulation of inflammation and immunity. The variants rs1126616 and rs9138 of this gene have been associated with the inflammatory response. The study aims to analyze the association of the rs1126616 and rs9138 variants of the SPP1 gene in SLE Mexican-Mestizo patients without LN (SLE-LN). In this cross-sectional study, a total of 171 genomic DNA samples from SLE patients were clinically confirmed, of which 111 were SLE without LN, 60 were SLE with LN, and 100 healthy individuals were included as reference group. The rs1126616 variant was genotyped using PCR-RFLPs, and the rs9138 variant was genotyped using qPCR TaqMan. The TT genotype, the recessive model [OR 2.76 (95% CI 1.31-5.82), p = 0.011], and the T allele [OR 2.0 (95% CI 1.26-3.16), p = 0.003] of the rs1126616 variant are risk factors for SLE with LN. By contrast, the rs9138 variant did not show statistically significant differences among SLE patients stratified by LN. In our study of SLE Mexican-Mestizo patients with and without NL, demographic and clinical characteristics do not differ from other SLE populations, and the TT genotype of the rs1126616 variant of the SPP1 gene confers a risk factor for the presentation of LN. Otherwise, the rs9138 variant did not show association with NL.

Sex Differences in the Atherogenic Risk Index in Healthy Mexican Population and Its Relationship with Anthropometric and Psychological Factors.

Dyslipidemia is a risk factor for cardiovascular disease and mortality; however, the association of this variable with a wide range of personal and psychological variables has not been researched. Therefore, the aim of this study was to compare lipid levels and anthropometric measures between sexes and to determine the association between personal and psychological variables with the atherogenic risk index (ARI). An adult population which auto-reported as healthy was invited to participate via social media and in person. They filled out a questionnaire with personal and psychological variables; in addition, the body mass index (BMI) and waist-to-hip ratio (WHR) were measured, and a blood sample was obtained to determine serum lipids. A total of 172 participants were included, from which 92 (53.49%) were women; both sexes were comparable in age and most sociodemographic values. Men showed significantly higher levels of total cholesterol, LDL cholesterol, triglycerides, ARI, and lower levels of HDL cholesterol. The men also showed higher values of WHR than the women. In the bivariate analysis, ARI showed the highest correlation with WHR (r = 0.664) in the men and with BMI (r = 0.619) in the women. In the multivariate analysis, the quality of food intake was negatively correlated with ARI in the global and women's samples, and the psychological variables of assertiveness and positive relations with others were negatively correlated with ARI in women, while purpose in life was negatively correlated with ARI in men. In conclusion, the higher levels of serum lipids and ARI in men can be explained by the higher values of WHR in this sex. Behavioral and psychological variables could be protective factors for high ARI.

Association of Depression, Anxiety, Stress and Stress-Coping Strategies with Somatization and Number of Diseases According to Sex in the Mexican General Population.

Somatization and number of diseases are interrelated variables, whose association with stress-coping strategies, according to sex, has not been investigated. Therefore, the aim of this study was to investigate such association in a sample of the Mexican general population. The general population was invited to answer an electronic questionnaire via the social networks-e-mail, WhatsApp and Facebook-by the research team. A sample of 1008 adults was obtained, of which 62.2% were women, in whom we detected higher levels of negative psychological variables, somatization and number of diseases and lower levels of sleep quality. Positive moderate correlations were found between depresion, anxiety and stress with somatization, on one hand, and with the number of diseases, on the other, and negative moderate correlations were found between sleep quality and the two dependent variables. As for the coping strategies, self-blame, behavioral disengagement, denial, self-distraction and substance use were positively correlated with somatization. Of these, self-blame, substance use, and self-distraction also showed a positive correlation with number of diseases in both sexes. Negative correlations were detected for active coping and the two dependent variables in men and for religion and planning with somatization in women. In conclusion, the coping strategies showed significant correlations with somatization and number of diseases in both sexes.

A paternal t(6;22)(q25.3;p12) leading to a deleted and satellited der(6) in a short-lived infant.

BACKGROUND: Non-acrocentric satellited chromosomes mostly result from familial balanced insertions or translocations with p12 or p13 of any acrocentric. Although all non-acrocentrics have been involved, only 12 instances of chromosome 6 involvement are known. CASE PRESENTATION: A female infant exhibited clinical features typical of 6qter deletions and also generalized hypertrichosis and synophrys, traits seldom reported in patients with similar imbalances or haploinsufficiency of ARID1B located in 6q25.3. She had a paternal derivative satellited 6q of a t(6;22)(q25.3;p12)pat entailing a 6q terminal deletion, karyotype 46,XX,der(6)t(6;22)(q25.3;p12)pat [16].ish del 6q subtel-. CONCLUSION: Male and female carriers of reciprocal translocations or insertions between chromosome 6 and the short arm of any acrocentric have few unbalanced offspring mostly by adjacent-1 segregation. In addition, spontaneous abortions or male infertility was present in 7/13 instances of satellited chromosome 6.

Williams-Beuren syndrome in Mexican patients confirmed by FISH and assessed by aCGH.

Williams-Beuren syndrome (WBS) has a prevalence of 1/7500-20000 live births and results principally from a de novo deletion in 7q11.23 with a length of 1.5 Mb or 1.8 Mb. This study aimed to determine the frequency of 7q11.23 deletion, size of the segment lost, and involved genes in 47 patients with a clinical diagnosis of WBS and analysed by fluorescence in situ hybridization (FISH); among them, 31 had the expected deletion. Micro-array comparative genomic hybridization (aCGH) confirmed the loss in all 18 positive-patients tested: 14 patients had a 1.5 Mb deletion with the same breakpoints at 7q11.23 (hg19: 72726578-74139390) and comprising 24 coding genes from TRIM50 to GTF2I. Four patients showed an atypical deletion: two had a 1.6 Mb loss encompassing 27 coding genes, from NSUN5 to GTF2IRD2; another had a 1.7 Mb deletion involving 27 coding genes, from POM121 to GTF2I; the remaining patient presented a deletion of 1.2 Mb that included 21 coding genes from POM121 to LIMK1. aCGH confirmed the lack of deletion in 5/16 negative-patients by FISH. All 47 patients had the characteristic facial phenotype of WBS and 45 of 47 had the typical behavioural and developmental abnormalities. Our observations further confirm that patients with a classical deletion present a typical WBS phenotype, whereas those with a high (criteria of the American Association of Pediatrics, APP) clinical score but lacking the expected deletion may harbour an ELN point mutation. Overall, the concomitant CNVs appeared to be incidental findings.

New subtype of familial achondrogenesis type IA (Houston-Harris).

BACKGROUND: Achondrogenesis is a skeletal dysplasia characterized primarily by short stature, severe micromelia, short and narrow chest, prematurity, polyhydramnios, fetal hydrops, and in utero or neonatal death. Based on the radiological and histopathological findings, there are three types of achondrogenesis: type 1A (Houston-Harris), type 1B (Fraccaro) and type 2 (Langer-Saldino). CLINICAL CASE: A premature female product was studied whose clinical, radiological and histopathological characteristics were compatible with achondrogenesis Type 1A. The family information allowed us to conclude that the 4 products of the 6 previous pregnancies were affected. Statistical analysis in at least 4 families previously described, including this family case showed significant differences between expected and observed number of members, being incongruent with an autosomal recessive mode of inheritance previously reported. CONCLUSIONS: therefore, it could be considered a new subtype of achondrogenesis type 1A due to the presence of a preferential germline mutation.

INTRODUCCIÓN: La acondrogénesis es una displasia esquelética que se caracteriza principalmente por talla baja, micromelia grave, tórax corto y estrecho, prematurez, polihidramnios, hidropesía fetal y muerte fetal in utero o neonatal. Según los hallazgos radiológicos e histopatológicos existen tres tipos de acondrogénesis: tipo 1A (Houston-Harris), tipo 1B (Fraccaro) y tipo 2 (Langer-Saldino). CASO CLÍNICO: Se sometió a estudio a un producto femenino prematuro cuyas características clínicas, radiológicas e histopatológicas fueron compatibles con acondrogénesis tipo 1A. La información familiar permitió concluir que los cuatro productos de los seis embarazos previos se encontraban afectados. El análisis estadístico en por lo menos cuatro familias previamente descritas, incluyendo este caso familiar, mostró diferencias significativas entre el número de miembros esperado y el observado, siendo incongruente con el modo de herencia autosómico recesivo previamente reportado. CONCLUSIONES: Podría considerarse un nuevo subtipo de acondrogénesis tipo 1A debida a la presencia de una mutación germinal preferencial.

miRNA-24 Gene Sequence, DHFR -829C-T Genotypes, and Methotrexate Response in Mexican Patients with Rheumatoid Arthritis.

AIM: The present study looked for variation in the miRNA-24 sequence, and evaluated the associations between the dihydrofolate reductase (DHFR) gene-829 C-T polymorphism and plasma DHFR concentrations with response to methotrexate (MTX) treatment in Mexican patients with rheumatoid arthritis (RA). METHODS: A total of 135 women with RA were classified as responders (disease activity score [DAS28] <3.2) or nonresponders to MTX (DAS28 > 3.2). We determined the genotype of the patients using the polymerase chain reaction-restriction fragment length polymorphism method. Plasma DHFR enzyme levels and mi-RNA24 sequences were assessed by enzyme-linked immunosorbent assay (ELISA) and Sanger sequencing, respectively. Allelic frequencies and the genotypic distribution of the polymorphism were analyzed by the chi-square test. RESULTS: The genotype frequencies of the DHFR -829C-T polymorphism among responders were 37.0% CC, 52.1% CT, and 10.9% TT and for nonresponders were 33.9% CC, 56.4% CT, and 9.7% TT. No significant differences in genotype frequencies were found between the groups (p = 0.88). The DHFR levels relative to genotype for responders were 6.8 ± 2.7, 6.1 ± 2.7, and 6.5 ± 1.5 ng/mL for CC, CT, and TT, respectively, and for nonresponders were 6.5 ± 2.0, 6.1 ± 3.1, and 7.4 ± 1.8 ng/mL for CC, CT, and TT, respectively. No significant differences were found between the two groups. Similarly, both groups showed no sequence variations in miRNA-24 gene. CONCLUSION: The -829C-T polymorphism of DHFR gene was not associated with response to MTX by RA patients, and no variations were found in the miRNA-24 sequence that might modify the response to treatment or DHFR enzyme levels in a Mexican population with RA.

New subtype of familial achondrogenesis type IA (Houston-Harris). / Nuevo subtipo de acondrogénesis familiar tipo IA (Houston-Harris)

Background: Achondrogenesis is a skeletal dysplasia characterized primarily by short stature, severe micromelia, short and narrow chest, prematurity, polyhydramnios, fetal hydrops, and in utero or neonatal death. Based on the radiological and histopathological findings, there are three types of achondrogenesis: type 1A (Houston-Harris), type 1B (Fraccaro) and type 2 (Langer-Saldino). Clinical case: A premature female product was studied whose clinical, radiological and histopathological characteristics were compatible with achondrogenesis Type 1A. The family information allowed us to conclude that the 4 products of the 6 previous pregnancies were affected. Statistical analysis in at least 4 families previously described, including this family case showed significant differences between expected and observed number of members, being incongruent with an autosomal recessive mode of inheritance previously reported. Conclusions: therefore, it could be considered a new subtype of achondrogenesis type 1A due to the presence of a preferential germline mutation.

Introducción: La acondrogénesis es una displasia esquelética que se caracteriza principalmente por talla baja, micromelia grave, tórax corto y estrecho, prematurez, polihidramnios, hidropesía fetal y muerte fetal in utero o neonatal. Según los hallazgos radiológicos e histopatológicos existen tres tipos de acondrogénesis: tipo 1A (Houston-Harris), tipo 1B (Fraccaro) y tipo 2 (Langer-Saldino). Caso clínico: Se sometió a estudio a un producto femenino prematuro cuyas características clínicas, radiológicas e histopatológicas fueron compatibles con acondrogénesis tipo 1A. La información familiar permitió concluir que los cuatro productos de los seis embarazos previos se encontraban afectados. El análisis estadístico en por lo menos cuatro familias previamente descritas, incluyendo este caso familiar, mostró diferencias significativas entre el número de miembros esperado y el observado, siendo incongruente con el modo de herencia autosómico recesivo previamente reportado. Conclusiones: Podría considerarse un nuevo subtipo de acondrogénesis tipo 1A debida a la presencia de una mutación germinal preferencial.

Determination of plasma lactate in the emergency department for the early detection of tissue hypoperfusion in septic patients.

OBJECTIVE: To determine the validity of plasma lactate in the emergency department for the early detection of tissue hypoperfusion in septic patients. MATERIALS AND METHODS: Longitudinal descriptive study. Non probabilistic sampling for convenience. Plasma lactate levels were determined in patients admitted to the emergency department with systemic inflammatory response data and clinical suspicion or documented infection. Follow-up was seven days. Complications were considered if the patients presented septic shock, severe sepsis, entry to intensive care or death. RESULTS: Ninety patients were included. The mean age was 57.4±20.31. Fifty five percent (n=49) were women. 25% (n=22) of the patients showed complications. Plasma lactate levels were 1.55mmol/L in uncomplicated patients and 3.72mmol/L for complicated patients (p<0.001). The area under the ROC curve was 0.72 (95% CI, 0.575-0.829). The cutoff point that best described the relationship with the probability of complications was that set at 4.2mmol/L. The variables studied that showed a significant association with the probability of complications were edema (p=0.004), and infections of the respiratory tract (p=0.037). A model that included lactate levels, using as adjustment variables edema and the presence of low respiratory tract infection explained between 0.234 and 0.349 of the dependent variant, correctly classifying 80% of the cases. CONCLUSION: Plasma lactate is useful in emergency departments as a predictive test for the early detection of patients with tissue hypoperfusion that evolve to severe sepsis, septic shock or death.

Identification of beta-Lactamases and beta-Lactam-Related Proteins in Human Pathogenic Bacteria using a Computational Search Approach.

A systematic analysis of beta-lactamases based on comparative proteomics has not been performed thus far. In this report, we searched for the presence of beta-lactam-related proteins in 591 bacterial proteomes belonging to 52 species that are pathogenic to humans. The amino acid sequences for 19 different types of beta-lactamases (ACT, CARB, CifA, CMY, CTX, FOX, GES, GOB, IMP, IND, KPC, LEN, OKP, OXA, OXY, SHV, TEM, NDM, and VIM) were obtained from the ARG-ANNOT database and were used to construct 19 HMM profiles, which were used to identify potential beta-lactamases in the completely sequenced bacterial proteomes. A total of 2877 matches that included the word "beta-lactamase" and/or "penicillin" in the functional annotation and/or in any of its regions were obtained. These enzymes were mainly described as "penicillin-binding proteins," "beta-lactamases," and "metallo-beta-lactamases" and were observed in 47 of the 52 species studied. In addition, proteins classified as "beta-lactamases" were observed in 39 of the species included. A positive correlation between the number of beta-lactam-related proteins per species and the proteome size was observed (R 0.78, P < 0.00001). This correlation partially explains the high presence of beta-lactam-related proteins in large proteomes, such as Nocardia brasiliensis, Bacillus anthracis, and Mycobacterium tuberculosis, along with their absence in small proteomes, such as Chlamydia spp. and Mycoplasma spp. We detected only five types of beta-lactamases (TEM, SHV, CTX, IMP, and OXA) and other related proteins in particular species that corresponded with those reported in the literature. We additionally detected other potential species-specific beta-lactamases that have not yet been reported. In the future, better results will be achieved due to more accurate sequence annotations and a greater number of sequenced genomes.

Influence of Anti-TNF and Disease Modifying Antirheumatic Drugs Therapy on Pulmonary Forced Vital Capacity Associated to Ankylosing Spondylitis: A 2-Year Follow-Up Observational Study.

OBJECTIVE: To evaluate the effect of anti-TNF agents plus synthetic disease modifying antirheumatic drugs (DMARDs) versus DMARDs alone for ankylosing spondylitis (AS) with reduced pulmonary function vital capacity (FVC%). METHODS: In an observational study, we included AS who had FVC% <80% at baseline. Twenty patients were taking DMARDs and 16 received anti-TNF + DMARDs. OUTCOME MEASURES: changes in FVC%, BASDAI, BASFI, 6-minute walk test (6MWT), Borg scale after 6MWT, and St. George's Respiratory Questionnaire at 24 months. RESULTS: Both DMARDs and anti-TNF + DMARDs groups had similar baseline values in FVC%. Significant improvement was achieved with anti-TNF + DMARDs in FVC%, at 24 months, when compared to DMARDs alone (P = 0.04). Similarly, patients in anti-TNF + DMARDs group had greater improvement in BASDAI, BASFI, Borg scale, and 6MWT when compared to DMARDs alone. After 2 years of follow-up, 14/16 (87.5%) in the anti-TNF + DMARDs group achieved the primary outcome: FVC% ≥80%, compared with 11/20 (55%) in the DMARDs group (P = 0.04). CONCLUSIONS: Patients with anti-TNF + DMARDs had a greater improvement in FVC% and cardiopulmonary scales at 24 months compared with DMARDs. This preliminary study supports the fact that anti-TNF agents may offer additional benefits compared to DMARDs in patients with AS who have reduced FVC%.

Homocisteína, polimorfismos MTHFR C677T, A1298C y variables clínico-bioquímicas en población mexicana / Homocysteine, MTHFR C677T and A1298C polymorphisms, and clinical and biochemical variables in the mexican population / Homocisteína, polimorfismos MTHFR C677T, A1298C e variáveis clínico-bioquímicas em população mexicana

El objetivo del trabajo consistió en analizar la relación del nivel sérico de homocisteína (Hcy) con los polimorfismos de la metilentetrahidrofolato reductasa MTHFR C677T y A1298C y variables clínicas y bioquímicas en población mexicana. Se determinó el nivel de Hcy (inmunoensayo) y de polimorfismos (PCR/RFLP) en 102 individuos de la población general. El genotipo 677TT mostró asociación significativa con el peso corporal (r=0,012) y el genotipo 1298CC tuvo tendencia a asociarse con el IMC (r~0,06). Los valores séricos de Hcy en mujeres (51/102) fueron 8,33±1,86 µmol/L y en hombres (51/102) 11,64±4,15 µmol/L. La Hcy mostró asociación positiva con peso corporal (r=0,004) y asociación negativa con Hb y Hto (r=0,001). Se encontró mayor nivel de Hcy en individuos fumadores (r=0,009) y una tendencia hacia hiperhomocisteinemia en alcohólicos y en mujeres menopáusicas. No se evidenció asociación de Hcy con los polimorfismos MTHFR C677T y A1298C, sin embargo, el análisis con el modelo de herencia dominante para el polimorfismo C677T (TT+CT vs. CC) mostró un efecto semidominante (r<0,10). En este estudio, la presencia de los polimorfismos MTHFR C677T y A1298C no representó ser un factor de riesgo significativo para hiperhomocisteinemia, sin embargo, se encontraron diferencias que puntualizan la posible dependencia de los niveles de Hcy en relación con los genotipos modificados con diversos factores ambientales.

The objective of the current work was to analyze the relationship of serum homocysteine (Hcy) with MTHFR C677T and A1298C polymorphisms and clinical and biochemical variables in the Mexican population. Hcy (immunoassay) levels and polymorphism (PCR/RFLP) levels were determined in 102 individuals from the general population. The 677TT genotype showed significant association with body weight (r=0.012) and the 1298CC genotype tended to be associated with BMI (r~0.06). Serum levels of Hcy in women (51/102) were 8.33±1.86 µmol/L and in men (51/102) 11.64± 4.15 µmol/L. The Hcy was positively as-sociated with body weight (r=0.004) and negatively with Hb and Hct (r=0.001). Higher levels of Hcy were found in smokers (r=0.009) and a tendency to hyperhomocysteinemia in alcoholics and in menopausal women. There was no association of Hcy with MTHFR C677T and A1298C polymorphisms, although the analysis with dominant inheritance model for the C677T polymorphism (TT + CT vs. CC) showed a semi-dominant effect (r<0.10). In this study, the presence of MTHFR C677T and A1298C polymorphisms did not represent a significant risk factor for hyperhomocysteinemia; however, those differences may point out the dependence of the relative levels of Hcy modifed genotypes on various environmental factors.

O objetivo deste trabalho foi analisar a relação do nível sérico de homocisteína (Hcy) com os polimorfismos da metilenotetrahidrofolato redutase MTHFR C677T e A1298C e variáveis clínicas e bioquímicas na po-pulação mexicana. Foi determinado o nível de Hcy (imunoensaio) e de polimorfismos (PCR/RFLP) em 102 indivíduos da população geral. O genótipo 677TT mostrou associação significativa com o peso corporal (r =0,012) e o genótipo 1298CC teve tendência a se associar com o IMC (r~0,06). Os níveis séricos de Hcy em mulheres (51/102) foram 8,33±1,86 µmol/L e em homens (51/102) 11,64±4,15 µmol/L. A Hcy mos-trou associação positiva com o peso corporal (r=0,004) e associação negativa com Hb e Hto (r=0,001). Encontraram-se níveis mais elevados de Hcy em fumantes (p=0,009) e uma tendência para hiperhomo-cisteinemia em alcoólatras e em mulheres na menopausa. Nenhuma associação se mostrou entre Hcy e os polimorfismos MTHFR C677T e A1298C, no entanto, a análise com modelo de herança dominante para o polimorfismo C677T (TT+CT vs. CC) mostrou um efeito semidominantes (r<0,10). Neste estudo, a presença dos polimorfismos MTHFR C677T e A1298C não representou ser um fator de risco significativo para a hiper-homocisteinemia, no entanto, foram encontradas diferenças que apontam a possível dependência dos níveis de Hcy relativos aos genótipos modificados com diversos fatores ambientais.

Homocisteína, polimorfismos MTHFR C677T, A1298C y variables clínico-bioquímicas en población mexicana / Homocysteine, MTHFR C677T and A1298C polymorphisms, and clinical and biochemical variables in the mexican population / Homocisteína, polimorfismos MTHFR C677T, A1298C e variáveis clínico-bioquímicas em populaþÒo mexicana

El objetivo del trabajo consistió en analizar la relación del nivel sérico de homocisteína (Hcy) con los polimorfismos de la metilentetrahidrofolato reductasa MTHFR C677T y A1298C y variables clínicas y bioquímicas en población mexicana. Se determinó el nivel de Hcy (inmunoensayo) y de polimorfismos (PCR/RFLP) en 102 individuos de la población general. El genotipo 677TT mostró asociación significativa con el peso corporal (r=0,012) y el genotipo 1298CC tuvo tendencia a asociarse con el IMC (r~0,06). Los valores séricos de Hcy en mujeres (51/102) fueron 8,33±1,86 Amol/L y en hombres (51/102) 11,64±4,15 Amol/L. La Hcy mostró asociación positiva con peso corporal (r=0,004) y asociación negativa con Hb y Hto (r=0,001). Se encontró mayor nivel de Hcy en individuos fumadores (r=0,009) y una tendencia hacia hiperhomocisteinemia en alcohólicos y en mujeres menopáusicas. No se evidenció asociación de Hcy con los polimorfismos MTHFR C677T y A1298C, sin embargo, el análisis con el modelo de herencia dominante para el polimorfismo C677T (TT+CT vs. CC) mostró un efecto semidominante (r<0,10). En este estudio, la presencia de los polimorfismos MTHFR C677T y A1298C no representó ser un factor de riesgo significativo para hiperhomocisteinemia, sin embargo, se encontraron diferencias que puntualizan la posible dependencia de los niveles de Hcy en relación con los genotipos modificados con diversos factores ambientales.(AU)

The objective of the current work was to analyze the relationship of serum homocysteine (Hcy) with MTHFR C677T and A1298C polymorphisms and clinical and biochemical variables in the Mexican population. Hcy (immunoassay) levels and polymorphism (PCR/RFLP) levels were determined in 102 individuals from the general population. The 677TT genotype showed significant association with body weight (r=0.012) and the 1298CC genotype tended to be associated with BMI (r~0.06). Serum levels of Hcy in women (51/102) were 8.33±1.86 Amol/L and in men (51/102) 11.64± 4.15 Amol/L. The Hcy was positively as-sociated with body weight (r=0.004) and negatively with Hb and Hct (r=0.001). Higher levels of Hcy were found in smokers (r=0.009) and a tendency to hyperhomocysteinemia in alcoholics and in menopausal women. There was no association of Hcy with MTHFR C677T and A1298C polymorphisms, although the analysis with dominant inheritance model for the C677T polymorphism (TT + CT vs. CC) showed a semi-dominant effect (r<0.10). In this study, the presence of MTHFR C677T and A1298C polymorphisms did not represent a significant risk factor for hyperhomocysteinemia; however, those differences may point out the dependence of the relative levels of Hcy modifed genotypes on various environmental factors.(AU)

O objetivo deste trabalho foi analisar a relaþÒo do nível sérico de homocisteína (Hcy) com os polimorfismos da metilenotetrahidrofolato redutase MTHFR C677T e A1298C e variáveis clínicas e bioquímicas na po-pulaþÒo mexicana. Foi determinado o nível de Hcy (imunoensaio) e de polimorfismos (PCR/RFLP) em 102 indivíduos da populaþÒo geral. O genótipo 677TT mostrou associaþÒo significativa com o peso corporal (r =0,012) e o genótipo 1298CC teve tendÛncia a se associar com o IMC (r~0,06). Os níveis séricos de Hcy em mulheres (51/102) foram 8,33±1,86 Amol/L e em homens (51/102) 11,64±4,15 Amol/L. A Hcy mos-trou associaþÒo positiva com o peso corporal (r=0,004) e associaþÒo negativa com Hb e Hto (r=0,001). Encontraram-se níveis mais elevados de Hcy em fumantes (p=0,009) e uma tendÛncia para hiperhomo-cisteinemia em alcoólatras e em mulheres na menopausa. Nenhuma associaþÒo se mostrou entre Hcy e os polimorfismos MTHFR C677T e A1298C, no entanto, a análise com modelo de heranþa dominante para o polimorfismo C677T (TT+CT vs. CC) mostrou um efeito semidominantes (r<0,10). Neste estudo, a presenþa dos polimorfismos MTHFR C677T e A1298C nÒo representou ser um fator de risco significativo para a hiper-homocisteinemia, no entanto, foram encontradas diferenþas que apontam a possível dependÛncia dos níveis de Hcy relativos aos genótipos modificados com diversos fatores ambientais.(AU)

The association between the 844ins68 polymorphism in the CBS gene and breast cancer.

INTRODUCTION: The cystathionine beta synthase (CBS) gene plays an important role in homocysteine metabolism because it catalyzes the first step of the transsulfuration pathway, during which homocysteine is converted to cystathionine. Polymorphisms of CBS have been associated with cancer. MATERIAL AND METHODS: We examined the role of the 844ins68 polymorphism by comparing the genotypes of 371 healthy Mexican women with the genotypes of 323 Mexican women with breast cancer (BC). RESULTS: The observed genotype frequencies for controls and BC patients were 1% and 2% for Ins/Ins, 13% and 26% for W/Ins, and 86% and 72% for W/W, respectively. We found that the odds ratio (OR) was 2.2, with a 95% confidence interval (95% CI) of 1.5-3.3, p = 0.0001. The association was also evident when comparing the distribution of the W/Ins-Ins/Ins genotypes in patients in the following categories: 1) menopause and high γ-glutamyltransferase (GGT) levels (OR of 2.17, 95% CI: 1.17-4.26, p = 0.02), 2) chemotherapy response and high lactate dehydrogenase (LDH) levels (OR 2.2, 95% CI: 1.08-4.4, p = 0.027), 3) chemotherapy response and high GGT levels (OR 2.46, 95% CI: 1.2-4.8, p = 0.007), and 4) body mass index (BMI) and III-IV tumor stage (OR 3.2, 95% CI: 1.2-8.3, p = 0.013). CONCLUSIONS: We conclude that the genotypes W/Ins-Ins/Ins of the 844ins68 polymorphism in the CBS gene contribute significantly to BC susceptibility in the analyzed sample from the Mexican population.

PADI4 haplotypes in association with RA Mexican patients, a new prospect for antigen modulation.

Peptidyl arginine deiminase IV (PAD 4) is the responsible enzyme for a posttranslational modification called citrullination, originating the antigenic determinant recognized by anti-cyclic citrullinated peptide antibodies (ACPA). Four SNPs (single nucleotide polymorphisms) have been described in PADI4 gene to form a susceptibility haplotype for rheumatoid arthritis (RA); nevertheless, results in association studies appear contradictory in different populations. The aim of the study was to analyze if the presence of three SNPs in PADI4 gene susceptibility haplotype (GTG) is associated with ACPA positivity in patients with RA. This was a cross-sectional study that included 86 RA patients and 98 healthy controls. Polymorphisms PADI4_89, PADI4_90, and PADI4_92 in the PADI4 gene were genotyped. The susceptibility haplotype (GTG) was more frequent in RA patients; interestingly, we found a new haplotype associated with RA with a higher frequency (GTC). There were no associations between polymorphisms and high scores in Spanish HAQ-DI and DAS-28, but we did find an association between RARBIS index and PADI4_89, PADI4_90 polymorphisms. We could not confirm an association between susceptibility haplotype presence and ACPA positivity. Further evidence about proteomic expression of this gene will determine its participation in antigenic generation and autoimmunity.

Effect of endovenous morphine vs. ketorolac on proinflammatory cytokines during postoperative analgesia in laparoscopic cholecystectomy.

BACKGROUND: Postoperative pain is the main symptom following a surgical event and is related to an inflammatory process involving cytokine secretion. This type of pain is usually treated with opioids such as morphine, whose analgesic efficacy is well known. However, it is unknown when compared with ketorolac in measuring proinflammatory cytokine levels. The aim of this study was to determine the postoperative analgesic effect with endovenous morphine on proinflammatory cytokine levels in patients who underwent laparoscopic choleystectomy. METHODS: We studied 40 patients who underwent laparoscopic cholecystectomy. Patients were randomized to receive morphine (0.05 mg/kg) or ketorolac (0.2 mg/kg) IV during gallbladder extraction and after the surgical event at the following dose: morphine (0.15 mg/kg) or ketorolac (0.7 mg/kg) for 40 min. Clinical evaluations included were hemodynamic, analgesic with visual analogue scale, and sedation (Ramsay scale). IL-1ß and TNF-a were measured pre- and postoperatively and after 12 h. Safety profile was evaluated with hemodynamic constants. Statistical analysis was carried out using Mann-Whitney U test and Fisher exact test. RESULTS: TNF-a was increased significantly in the immediate postoperative period and after 12 h in the morphine group. IL-1ß was not detected preoperatively, in the immediate postoperative period and 12 h after surgery the levels were similar in both groups. The main adverse event was respiratory depression, which occurred in the morphine group. CONCLUSIONS: Proinflammatory cytokines were increased after surgery, particularly TNF-a in the group receiving morphine. The use of morphine is safe postoperatively.

[Deficiency of adenosine desaminase (ADA): clinical, biochemical, molecular and treatment aspects]. / Deficiencia de adenosina desaminasa (ADA): aspectos clínicos, bioquímicos, moleculares y de tratamiento.

Adenosine Desaminase (ADA) deficiency, is a purine metabolic disorder that cause severe combined immunodeficiency (SCID) due to the accumulation of toxic metabolites that primarily affects development, differentiation and function of T and B lymphocytes. In addition, some patients show neurological, renal and liver abnormalities, delayed in development, deafness and seizures. If the immune response is not restored, children with this disorder rarely survive; therefore, ADA deficiency must be suspected when difficulty gaining weight, recurrent infections and skeletal abnormalities are present. The ADA deficiency has clinical and immunological characteristics not seen in other immunodeficiencies, data that helps to guide the diagnosis and therapy. This review summarizes clinical, pathological, molecular and treatment findings described in this disease.

47,XXX/45,X/46,XX mosaicism in a patient with Turner phenotype and spontaneous puberal development.

OBJECTIVE: To describe a patient with infertility and phenotypic combination of Turner and triple-X syndrome related to mos 47,XXX/45X/46,XX karyotype. DESIGN: Case report. SETTING: División de Genética, Centro de Investigación Biomédica de Occidente and Hospital de Ginecología y Obstetricia, CMNO, Instituto Mexicano del Seguro Social. PATIENT(S): The 24-year-old patient presented a phenotypic combination of Turner syndrome and X polysomy. She showed wide and short neck, low posterior hairline, cubitus valgus, bilateral shortening of the fourth and fifth metacarpals, multiple nevi, and müllerian anomalies but had spontaneous pubarche, thelarche, and menarche. INTERVENTION(S): Laboratory evaluations, imaging studies, ovarian biopsy, G-banding karyotype, and in situ fluorescence hybridization. MAIN OUTCOME MEASURE(S): Clinical and laboratory findings. RESULT(S): A karyotype: mos 47,XXX/45X/46,XX was found in the cytogenetic studies, a bicornuate uterus in the ultrasonographic scan, and a normal ovarian profile in the laboratory tests. CONCLUSION(S): The infertility in the present case can be related to either bicornuate uterus or subclinical abortions due to aneuploid ova. Cytogenetic assessment provides important information regarding infertile patients with uterine factors and short stature.

[Fcgamma receptor polymorphisms and systemic lupus erythematosus]. / Polimorfismos de los receptores fcgamma y lupus eritematoso sistémico.

The G Immunoglobulin Fc Receptors (FcgammaR) belong to the TNFR5 receptors family, of the immunoglobulin superfamily and are widely expressed in the immune system; their function follows in importance after the complement receptors for immunocomplexes clearance. On the other hand, the systemic lupus erythematosus (SLE) is the prototype of the autoimmune diseases mediated by immunocomplexes and several studies have shown an impaired handle of these ones in part due to dysfunction of the FcgammaR. Among all types of Fcgamma receptors, the FcgammaRIIA, FcgammaRIIB, FcgammaRIIIA and FcgammaRIIIB have well characterized polymorphisms that produce an alteration in the receptor function. A number of studies have been done worldwide to probe an association between these polymorphism and SLE or some of its clinical features, among these the most important are two meta-analyses in which it is shown that the FcygammaRIIA-R131 polymorphism present a significant association with SLE susceptibility (OR: 1.3, 95% CI: 1.10-1.52), while the FcgammaRIIIA F176 polymorphism showed to be associated with lupic nephritis (OR: 1.47, 95% CI: 1.11-1.93, p = 0.006) but not with SLE susceptibility, the results in the rest of the polymorphisms studied are still contradictories.