José Alfredo Sierra-Ramírez

Single nucleotide polymorphisms of the FTO gene and cancer risk: an overview

The FTO (fat mass and obesity-associated) gene has a strong linkage disequilibrium block, within which SNPs have been identified that are involved in the development of obesity. Recently some of these variants have also been associated with cancer. However, identification of the possible mechanisms that could explain these associations has proven to be elusive. It has been found that FTO polymorphisms can regulate the expression of genes at large kilobases of distance as well as the expression of the FTO gene itself, and regions for transcription factor binding. To date it has been observed that variants rs9939609, rs17817449, rs8050136, rs1477196, rs6499640, rs16953002, rs11075995 and rs1121980 are associated with the risk of developing cancer. Some studies have produced negative results when comparing the same polymorphisms, but make a simple association between polymorphic variants and cancer, have proved difficult because this relation is by nature multifactorial. A certain degree of variation resulting from the improper design of studies or processing of data can lead to erroneous conclusions. However, it is now unquestionable that certain FTO polymorphisms regulate genetic expression related to cancer susceptibility, although this field is just beginning to be understood.

Effect on risk of anencephaly of gene-nutrient interactions between methylenetetrahydrofolate reductase C677T polymorphism and maternal folate, vitamin B12 and homocysteine profile.

OBJECTIVE To evaluate the effects on anencephaly risk of the interaction between the maternal profile of folate, vitamin B12 and homocysteine and the 677C→T polymorphism in the gene encoding methylenetetrahydrofolate reductase (MTHFR). DESIGN Case-control study paired (1:1) on maternity clinic, date of birth and state of residence. Cases of anencephaly were identified using the Registry of the Mexican Neural Tube Defect Epidemiological Surveillance System. Case and control mothers were selected from the same maternity departments. All mothers completed a structured questionnaire and blood samples were obtained to determine the MTHFR 677C→T polymorphism and biochemical profile. SETTING Mexico, Puebla and Guerrero states, Mexico. SUBJECTS A total of 151 mothers of cases and controls were enrolled from March 2000 to February 2001. We had complete information on biochemical profile and MTHFR C677T polymorphism for ninety-eight mothers of cases and ninety-one mothers of controls. RESULTS The adjusted models show that the risk of anencephaly in mothers with 677TT genotype was reduced by 18 % (OR = 0·82; 95 % CI 0·72, 0·94) for each 1 ng/ml increment in serum folate. In terms of tertiles, mothers with 677TT genotype with serum folate levels in the upper tertile (>14·1 ng/ml) had a 95 % lower risk to have a child with anencephaly than mothers with serum folate levels in the first and second tertiles (P trend = 0·012). CONCLUSIONS Our data agree with the hypothesis of a gene-nutrient interaction between MTHFR 677C→T polymorphism and folate status. We observed a protective effect on anencephaly risk only in mothers with 677TT genotype as serum folate levels increased.

Polimorfismo 677CT del gen de la metilentetradihidrofolato reductasa y cardiopatias congenitas aisladas en poblacion mexicana

INTRODUCTION AND OBJECTIVES The frequency of the 677C>T mutation in the methylenetetrahydrofolate reductase gene in Mexico is one of the highest worldwide. Some studies have shown that both the homozygous state of this mutation and a high homocysteine concentration are associated with congenital heart disease. The aim of this study was to determine whether this association exists in the Mexican population. METHODS Genotypes were analyzed in 60 patients with congenital heart disease and in their mothers, and the levels of homocysteine were determined in the latter group. The genotypes were compared with those of a control group (n=62) and of their mothers. All the possible mother-child genotype combinations were also compared. RESULTS There were no significant differences in allele or genotype frequencies between the patients with congenital heart disease and the controls or their respective mothers (P>.05). Although no significant differences were observed when the homocysteine concentrations in the presence of the CC or the TT genotype were compared, a clear trend was observed (P=.0621). We found no significant differences in homocysteine concentrations in relation to folic acid intake. The study cases and controls did not differ in terms of the possible combinations of mother-child genotypes. CONCLUSIONS The frequencies obtained were consistent with those reported for Mexico. No significant differences were found between groups. Nor did we find any association between TT mutations in both the mother and child and hyperhomocysteinemia. There was no evidence of an association between any of the mother-child genotype combinations and congenital heart disease. Similar studies with larger numbers of patients are required to confirm or refute some of the trends observed in this report.

Comparative pharmacokinetics and pharmacodynamics after subcutaneous and intramuscular administration of medroxyprogesterone acetate (25 mg) and estradiol cypionate (5 mg)

BACKGROUND The efficacy of contraceptives is affected by its route and ease of administration. Herein, both pharmacokinetics and pharmacodynamics of the once-a-month combined injectable contraceptive medroxyprogesterone acetate (MPA) plus estradiol cypionate (E(2)-Cyp) were compared after intramuscular (IM) or subcutaneous (SC) injection in women of reproductive age. STUDY DESIGN Thirty women were randomly assigned to the SC (n=15) or IM (n=15) route of MPA 25 mg+E(2)-Cyp 5 mg administration. Serum samples were obtained daily for 7 days and then three times a week for 40 days in order to quantify E(2), progesterone and MPA. In addition, three ultrasounds were performed on each subject to determine follicular development, and a daily record of the bleeding pattern and side effects was maintained. RESULTS A comparative analysis showed that the main pharmacokinetic (peak serum concentration, peak serum time, area under the serum concentration vs. time curve, absorption half-life and elimination half-life) and pharmacodynamic parameters, such as follicular development and ovulation, were similar in the SC vs. IM groups. Complete suppression in ovarian function was present in all women. The bleeding patterns and side effects were similar in both groups. CONCLUSIONS The results presented herein demonstrate that the injection of 25 mg of MPA plus 5 mg of E(2)-Cyp has similar efficacy and safety with either the SC or IM route of administration. The SC option can be considered a viable self-administered contraceptive option that might increase womens compliance to contraceptive use.

Acoustic Analysis and Electroglottography in Elite Vocal Performers

BACKGROUND Acoustic analysis of voice (AAV) and electroglottography (EGG) have been used for assessing vocal quality in patients with voice disorders. The effectiveness of these procedures for detecting mild disturbances in vocal quality in elite vocal performers has been controversial. OBJECTIVE To compare acoustic parameters obtained by AAV and EGG before and after vocal training to determine the effectiveness of these procedures for detecting vocal improvements in elite vocal performers. MATERIALS AND METHODS Thirty-three elite vocal performers were studied. The study group included 14 males and 19 females, ages 18-40 years, without a history of voice disorders. Acoustic parameters were obtained through AAV and EGG before and after vocal training using the Linklater method. RESULTS Nonsignificant differences (P > 0.05) were found between values of fundamental frequency (F0), shimmer, and jitter obtained by both procedures before vocal training. Mean F0 was similar after vocal training. Jitter percentage as measured by AAV showed nonsignificant differences (P > 0.05) before and after vocal training. Shimmer percentage as measured by AAV demonstrated a significant reduction (P < 0.05) after vocal training. As measured by EGG after vocal training, shimmer and jitter were significantly reduced (P < 0.05); open quotient was significantly increased (P < 0.05); and irregularity was significantly reduced (P < 0.05). CONCLUSIONS AAV and EGG were effective for detecting improvements in vocal function after vocal training in male and female elite vocal performers undergoing vocal training. EGG demonstrated better efficacy for detecting improvements and provided additional parameters as compared to AAV.

Impact of D-bifunctional Protein Deficiency on Telomere Length and Gene Expression in a Child

Aim: To explore, in one patient, the possibility that D-bifunctional protein (D-BP) deficiency affects telomere length, and to determine the profile of genetic expression. Presentation of Case: Due to the symptoms of a newborn and his family background, a peroxisomal panel was performed. There were high levels of very long chain fatty acids and abnormal peroxisomes. At 8 months the patient exhibited other complications, including progressive multi systemic deterioration, and at 15 months died of pneumonia. Discussion: Analysis of the patient’s fibroblasts provided evidence of a defect in the peroxisomes and in the oxidation of fatty acids, leading to a diagnosis of D-BP deficiency. Significant alterations were found in the genetic expression profile, with the