Longitudinal effects of FTO gene polymorphism on body composition, cardiorespiratory fitness, physical activity, inflammatory markers, and cardiovascular risk in children and adolescents. "The UP & DOWN study".

The role of polymorphism rs9939609 of the FTO gene has been related with fat mass and cardiovascular risk in adults, but it remains unclear in children and adolescents. Hence, the main aim of this study was to determine the FTO polymorphism effects on body composition, cardiorespiratory fitness (CRF), physical activity (PA), inflammatory markers, and cardiovascular risk both in cross-sectional analysis and after two-years of follow-up in children and adolescents. A total of 2129 participants were included in this study. The rs9939609 polymorphism was genotyped. Body composition measurements, CRF, and moderate-to-vigorous PA (MVPA) were determined at baseline and after two-year of follow-up. Moreover, plasma leptin and adiponectin were also determined as inflammatory markers. Furthermore, an index of cardiovascular disease risk factors (CVDRF-I) was calculated. Codominant (TT vs. TA vs. AA) and dominant (AA+AT vs. TT) models were applied for statistical analysis. The results showed a main effect of the FTO genotype on body composition measures in both first and third year (p < 0.05), with lower adiposity in TT compared with AA or AA+AT group. These differences were maintained after accounting for pubertal maturity, sex, age, VO2 max, and MVPA. Moreover, lower leptin level was observed in TT compared to AA+AT group in the third year. An interaction in Gene*Time*Sex was found in height and neck circumference in dominant model (p = 0.047; p = 0.020, respectively). No differences were found in CRF, MVPA nor CVDRF-I between groups. Hence, homozygous TT allele could be a protective factor against weight gain from early childhood.

Impact of the FTO Gene Variation on Appetite and Fat Oxidation in Young Adults.

The FTO rs9939609 gene, which presents three polymorphisms (AA, AT, and TT), has been associated with the development of obesity through an increased fat accumulation; however, the associations of the gene with other physiological mechanisms, such as appetite or fat oxidation, are still unclear. Therefore, this study aims to evaluate the influence of the FTO rs9939609 gene on different obesity-related factors in young adults. The FTO rs9939609 polymorphism was genotyped in 73 participants (28 women, 22.27 ± 3.70 years). Obesity-related factors included dietary assessment, physical activity expenditure, body composition, appetite sensation, resting metabolic rate, maximal fat oxidation during exercise (MFO), and cardiorespiratory fitness. Our results showed that TT allele participants expressed higher values of hunger (p = 0.049) and appetite (p = 0.043) after exercising compared to the AT allele group. Moreover, the TT allele group showed significantly higher values of MFO (p = 0.031) compared to the AT group, regardless of sex and body mass index. Thus, our results suggest that the FTO rs9939609 gene has an influence on appetite, hunger, and fat oxidation during exercise, with TT allele participants showing significantly higher values compared to the AT allele group. These findings may have practical applications for weight loss and exercise programs.

Susceptibility to hepatitis B virus infection in adults living in Spain.

BACKGROUND: A protective hepatitis B virus (HBV) vaccine has been available for four decades. Universal HBV vaccination of infants is recommended by the WHO since the 1990s. Furthermore, HBV immunization is advised for all adults with high-risk behaviours and no seroprotection. However, HBV vaccine coverage remains globally suboptimal. The advent of new more efficacious trivalent HBV vaccines has renewed the interest in HBV vaccination. At present, the extent of current HBV susceptibility in adults remains unknown in Spain. METHODS: HBV serological markers were assessed on a large and representative sample of adults in Spain, including blood donors and individuals belonging to high-risk groups. Serum HBsAg, anti-HBc and anti-HBs were tested in specimens collected during the last couple of years. RESULTS: From 13 859 consecutive adults tested at seven cities across the Spanish geography, overall 166 (1.2%) had positive HBsAg. Past HBV infection was recognized in 14% and prior vaccine immunization in 24%. Unexpectedly, 37% of blood donors and 63% of persons belonging to high-risk groups had no serum HBV markers and therefore were potentially HBV susceptible. CONCLUSION: Roughly 60% of adults living in Spain seem to be HBV susceptible. Waning immunity might be more common than expected. Hence, HBV serological testing should be performed at least once in all adults regardless of risk exposures. HBV vaccine full courses or boosters should be administered to all adults lacking serological evidence of HBV protection.

Influence of Peroxisome Proliferator-Activated Receptor (PPAR)-gamma Coactivator (PGC)-1 alpha gene rs8192678 polymorphism by gender on different health-related parameters in healthy young adults.

This study aimed to analyze the influence of the peroxisome proliferator-activated receptor (PPAR)-gamma coactivator (PGC)-1 alpha (PPARGC1A) gene rs8192678 C>T polymorphism on different health-related parameters in male and female young adults. The PPARGC1A gene rs8192678 polymorphism was ascertained by polymerase chain reaction in 74 healthy adults (28 women; 22.72 ± 4.40 years) from Andalusia (Spain). Health-related variables included cardiometabolic risk, anthropometry and body composition, biochemical parameters, insulin sensitivity (QUICKI and HOMA-IR indexes), blood pressure (BP) at rest and after exercise, diet, basal metabolism, physical activity, maximal fat oxidation, and cardiorespiratory fitness. Our results showed differences by PPARGC1A gene rs8192678 C>T polymorphism in body mass (p = 0.002), body mass index (p = 0.024), lean body mass (p = 0.024), body fat (p = 0.032), waist circumference (p = 0.020), and BP recovery ratio (p < 0.001). The recessive model (CC vs. CT/TT) showed similar results but also with differences in basal metabolism (p = 0.045) and total energy expenditure (p = 0.024). A genotype*sex interaction was found in the QUICKI index (p = 0.016), with differences between CC and CT/TT in men (p = 0.049) and between men and women inside the CT/TT group (p = 0.049). Thus, the PPARGC1A gene rs8192678 C>T polymorphism is associated with body composition, basal metabolism, total energy expenditure, and BP recovery, where the CC genotype confers a protective effect. Moreover, our study highlighted sexual dimorphism in the influence of PPARGC1A gene rs8192678 C>T polymorphism on the QUICKI index.

Hepatitis C hospitalizations in Spain and impact of new curative antiviral therapies.

Chronic hepatitis C virus (HCV) infection is major cause of decompensated cirrhosis and liver cancer. The advent of curative new antiviral therapies since year 2015 has dramatically improved the prognosis of HCV patients. The real-life clinical benefits at country level of these therapies have not yet been assessed. This is a retrospective study of all hospitalizations in Spain including HCV as diagnosis using the Spanish National Registry of Hospital Discharges. Information was retrieved from 1997 to 2019. From 81,482,509 nationwide hospital admissions recorded during the study period, 1,057,582 (1.29%) included HCV as diagnosis. The median age of HCV hospitalized patients was 54 years old. Males accounted for 63.2% of cases. Most HCV admissions recorded chronic hepatitis C whereas acute hepatitis C was reported in less than 3%. In-hospital death occurred in 6.4% of HCV admissions. Coinfection with HIV or hepatitis B virus was seen in 14.8% and 6.4%, respectively. Patients hospitalized with HIV-HCV coinfection represented 14.8% of cases and were on average 17 years younger than HCV-monoinfected individuals. The rate of HCV hospitalizations significantly increased until 2005, and then stabilized for one decade. A significant reduction was noticed since 2015. However, whereas the proportion of HCV-associated hepatic decompensation events declined since then, liver cancer diagnoses increased. In conclusion, hospital admissions of HCV individuals significantly declined in Spain since 2015 following a wide prescription of new oral direct-acting antivirals. This reduction was primarily driven by a fall of hepatic decompensation events whereas HCV-related liver cancer continues rising.

The unexpected high prevalence of HBV subgenotype D4 in patients with chronic hepatitis B in Galicia, a northwestern Spanish region, reflects strong links with Latin America.

BACKGROUND: Hepatitis B virus (HBV) comprises 9 genotypes and multiple subgenotypes that depict differences in geographic distribution, clinical outcome and response to antiviral therapy. However, the molecular epidemiology of HBV geno/subgenotypes is globally scarce. In Spain, HBV genotype D seems to be more prevalent in the northwestern regions compared to the rest of the country for unclear reasons. METHODS: HBV genotyping was performed using geno2pheno on a S gene fragment amplified from plasma collected from all chronic hepatitis B individuals attended at one reference hospital in Santiago de Compostela, the Galicia's capital town. Phylogenetic and phylogeographic analyses using a fragment of 345 bp were performed in all viremic specimens. To avoid misleading allocation as consequence of short fragment analysis, several bioinformatic controls were used. RESULTS: A total of 320 individuals with persistent serum HBsAg+ and detectable HBV-DNA were seen between 2000 and 2016 (male 68.4%; median age, 52 years-old; native Spaniards 83.8%). HBV genotype distribution was as follows: A 15.3%; B 1.6%; C 2.5%; D 71.6%; E 3.1%; F 2.2%; G 3.1%; and H 0.6%. HBV genotype D was mostly represented by D4 and D2 subgenotypes (33.4% and 15% of total, respectively). Compared to chronic hepatitis B patients with genotypes B, C, E and G, HBV-D4 carriers tended to be older (54.2% had >50 years-old) and HBeAg-negative (85%). Moreover, 43% were female, 4.7% had cirrhosis, 10.2% hepatitis C and 6.4% HIV coinfection. Phylogenetic analyses could be performed on 82 HBV-D4 specimens; and 79 were confirmed as HBV-D4 using PhyML. Phylogeography using FasTree suggested at least two distinct introductions of HBV-D4 in Galicia, one from the Caribbean and South America, and another from India. CONCLUSIONS: HBV subgenotype D4 is the most prevalent HBV variant in chronic hepatitis B patients living in the northwest of Spain, representing 33.4% (107/320) of all chronic hepatitis B infections. This rate of HBV-D4 is among the highest reported worldwide. Epidemiological and phylogenetic analyses suggest a strong association with historical migrant exchanges with Latin America, and especially with the Caribbean basin.

Trends in hospitalizations and deaths in HIV-infected patients in Spain over two decades.

BACKGROUND: The prognosis of HIV infection dramatically improved after the introduction of triple antiretroviral therapy 25 years ago. Herein, we report the impact of further improvements in HIV management since then, looking at all hospitalizations in persons with HIV (PWH) in Spain. METHODS: A retrospective study using the Spanish National Registry of Hospital Discharges. Information was retrieved since 1997-2018. RESULTS: From 79 647 783 nationwide hospital admissions recorded during the study period, 532 668 (0.67%) included HIV as diagnosis. The mean age of PWH hospitalized increased from 33 to 51 years (P < 0.001). The rate of HIV hospitalizations significantly declined after 2008. Comparing hospitalizations during the first (1997-2007) and last (2008-2018) decades, the rate of non-AIDS illnesses increased, mostly due to liver disease (from 35.9 to 38.3%), cardiovascular diseases (from 12.4 to 28.2%), non-AIDS cancers (from 6.4 to 15.5%), and kidney insufficiency (from 5.4 to 13%). In-hospital deaths occurred in 5.5% of PWH, declining significantly over time. Although most deaths were the result from AIDS conditions (34.8%), the most frequent non-AIDS deaths were liver disease (47.1%), cardiovascular events (29.2%), non-AIDS cancers (24.2%), and kidney insufficiency (20.7%). CONCLUSION: Hospital admissions in PWH significantly declined after 2008, following improvements in HIV management and antiretroviral therapy. Non-AIDS cancers, cardiovascular events and liver disease represent a growing proportion of hospital admissions and deaths in PWH.

Influence of ACE Gene I/D Polymorphism on Cardiometabolic Risk, Maximal Fat Oxidation, Cardiorespiratory Fitness, Diet and Physical Activity in Young Adults.

There is controversy about the relationship between ACE I/D polymorphism and health. Seventy-four healthy adults (n = 28 women; 22.5 ± 4.2 years) participated in this cross-sectional study aimed at determining the influence of ACE I/D polymorphism, ascertained by polymerase chain reaction, on cardiometabolic risk (i.e., waist circumference, body fat, blood pressure (BP), glucose, triglycerides, and inflammatory markers), maximal fat oxidation (MFO), cardiorespiratory fitness (maximal oxygen uptake), physical activity and diet. Our results showed differences by ACE I/D polymorphism in systolic BP (DD: 116.4 ± 11.8 mmHg; ID: 116.7 ± 6.3 mmHg; II: 109.4 ± 12.3 mmHg, p = 0.035) and body fat (DD: 27.3 ± 10.8%; ID: 22.6 ± 9.7%; II: 19.3 ± 7.1%, p = 0.030). Interestingly, a genotype*sex interaction in relativized MFO by lean mass (p = 0.048) was found. The DD polymorphism had higher MFO values than ID/II polymorphisms in men (8.4 ± 3.0 vs. 6.5 ± 2.9 mg/kg/min), while the ID/II polymorphisms showed higher R-MFO values than DD polymorphism in women (6.6 ± 2.3 vs. 7.6 ± 2.6 mg/kg/min). In conclusion, ACE I/D polymorphism is apparently associated with adiposity and BP, where a protective effect can be attributed to the II genotype, but not with cardiorespiratory fitness, diet and physical activity. Moreover, our study highlighted that there is a sexual dimorphism in the influence of ACE I/D gene polymorphism on MFO.

Third wave of COVID-19 in Madrid, Spain.

A third wave of COVID-19 occurred after Christmas 2020 in Madrid, one of the European pandemic epicenters. We noticed 6 major differential features to previous waves. First, household contacts were a large proportion of cases. Second, access to rapid antigen tests allowed prompt diagnosis and isolation. Third, clinically severe cases and mortality rates were lower. Fourth, the more transmissible B.1.1.7 strain was increasingly found. Fifth, vaccination benefits were seen in healthcare workers and nursing homes. Lastly, reinfections were more common. By Easter 2021, approximately 25% of the population in Madrid had been infected with SARS-CoV-2. Therefore, massive and accelerated vaccination campaigns are warranted to prevent new COVID-19 waves.

Main differences between the first and second waves of COVID-19 in Madrid, Spain.

BACKGROUND: The emergence and rapid global spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) represents a major challenge to health services, and has disrupted social and economic activities worldwide. In Spain, the first pandemic wave started in mid-March 2020 and lasted for 3 months, requiring home confinement and strict lockdown. Following relaxation of the measures during the summer, a second wave commenced in mid-September 2020 and extended until Christmas 2020. METHODS: The two pandemic waves were compared using information collected from rapid diagnostic tests and polymerase chain reaction assays at one university clinic in Madrid, the epicentre of the pandemic in Spain. RESULTS: In total, 1569 individuals (968 during the first wave and 601 during the second wave) were tested for SARS-CoV-2-specific antibodies using fingerprick capillary blood. In addition, during the second wave, 346 individuals were tested for SARS-CoV-2-specific antigen using either oral swabs or saliva. The overall seroprevalence of first-time-tested individuals was 12.6% during the first wave and 7.7% during the second wave (P < 0.01). Seroconversions and seroreversions within 6 months occurred at low rates, both below 5%. During the second wave, 3.5% of tested individuals were SARS-CoV-2 antigen positive, with two cases considered as re-infections. Severe clinical symptoms occurred in a greater proportion of cases during the first wave compared with the second wave (27.8% vs 10.6%, respectively; P = 0.03). CONCLUSION: The cumulative seroprevalence of SARS-CoV-2 antibodies in Madrid at the end of 2020 was approximately 20%. Seroreversions within 6 months occurred in 4% of cases. Seroconversions and re-infections were clinically less severe during the second wave than during the first wave. Hypothetically, a lower viral inoculum as a result of social distancing, increased use of face masks, promotion of outdoor activities and restrictions on gatherings may have contributed to this lower pathogenicity.

Occult hepatitis B and HIV infection.

INTRODUCTION: Occult hepatitis B virus (HBV) infection, so-called occult B infection (OBI), is defined by the recognition of HBV-DNA in the absence of serum hepatitis B surface antigen (HBsAg). The HBV-DNA genome in OBI is fully replication competent and produced in the liver, characteristically with low-level HBV-DNA fluctuations in the bloodstream. The OBI status remains between chronic (HBsAg +) and resolved (anti-HBs +) phases in the natural history of HBV infection. METHODS: The clinical interest in OBI has increased because of its potential for overt HBV reactivation under immunosuppression as well as for HBV transmission, well established in recipients of blood transfusions and/or organ transplants. RESULTS: Given the shared transmission routes for HIV and HBV, earlier reports claimed that OBI was more frequent in AIDS patients. By contrast, the current scenario shows that OBI is negligible in the HIV population. One explanation is that HBV immunization and recall vaccination campaigns have been very active in this group. A second and most important reason points to the wide use of antiretroviral regimens that include anti-HBV active agents, that is, tenofovir, lamivudine, and/or emtricitabine. They are recommended either as treatment for all HIV carriers or as pre-exposure prophylaxis for uninfected individuals at risk. The consequences are that HBV reactivations associated with HIV-related immunodeficiency have become very rare. Furthermore, HBV suppression with these antivirals has markedly reduced the likelihood of transmission from OBI carriers and/or acquisition by uninfected exposed individuals. CONCLUSION: Enthusiasm unabated, however, new tenofovir-sparing antiretroviral regimens are becoming popular and might account for a resurgence of OBI in the HIV setting.

Association of HTR2A-1438G/A Genetic Polymorphism With Smoking and Chronic Obstructive Pulmonary Disease.

INTRODUCTION: Cigarette smoking is a major risk factor in the development of chronic obstructive pulmonary disease (COPD). Serotonin levels have been associated with COPD and smoking has been as a significant modulator. Elevated levels of serotonin are responsible for bronchoconstriction and pulmonary vasoconstriction and also nicotine dependence, thus serotonin response could be affected by genetic polymorphisms in transporters and receptors of serotonin. OBJECTIVES: The aim of the current study was to analyze the effect of SLC6A4 (5HTT_LPR) (rs25531) and HTR2A-1438G/A (rs6311) genetic polymorphisms on the relation between smoking habits and COPD. METHODS: The association between SLC6A4 (5HTT_LPR) (rs25531), HTR2A-1438G/A (rs6311), smoking degree and COPD was analyzed in a total of 77 COPD patients (active smokers) and 90 control subjects (active healthy smokers). The DNA was extracted of peripheral leukocytes samples and genotyping was performed using an allele specific polymerase chain reaction. RESULTS: The distribution of SLC6A4 genotypes did not vary between healthy smokers and COPD patients (P=0.758). On the other hand, the A allele of HTR2A (rs6311) was significantly associated with COPD incidence in the trend model (P=0.02; 1.80 [1.04-3.11]). Among all smokers, this allele was also associated with the number of pack years smoked (P=0.02) and also, we observed a marginal association with FEV1/FVC values (P=0.06). CONCLUSION: Our results point a possible role of the A allele of HTR2A (rs6311) in COPD pathogenesis, suggesting that this effect depends partly on tobacco consumption due to a gene-by-environment interaction.

Red Bull® energy drink increases consumption of higher concentrations of alcohol.

Mixing alcohol with caffeinated energy drinks is a common practice, especially among young people. In humans, the research on this issue has mainly focused on the use of the mass-marketed energy drinks themselves, whereas in animal models, it has focused on the individual effects of their active ingredients (i.e. caffeine). Here, we have characterized how Red Bull®, one of the most consumed caffeinated energy drink worldwide, modulates operant alcohol self-administration in Wistar rats. We found that animals readily and steadily responded for Red Bull (mean: 90 responses, 30 minutes and fixed-ratio 1), which was accompanied by locomotor stimulating effects (26 percent increase). The higher the concentration of alcohol (3-20 percent), the higher the consumption of alcohol (g/kg) and associated blood alcohol levels (91.76 percent) in the mixed Red Bull-alcohol group (60 percent increase). Blood caffeine levels in the Red Bull group were 4.69 µg/ml and 1.31 µg/ml in the Red Bull-alcohol group after the 30-minute session. Because Red Bull also contains 11 percent sucrose, we examined the time course of blood glucose as well as insulin and corticosterone. The correlation between intake of Red Bull and blood glucose levels was higher at 90 minutes than 5 minutes after its consumption, and there was no relationship with blood insulin or blood corticosterone levels. Red Bull did not alter extinction and reacquisition of responding for alcohol nor did it affect relapse-like drinking. Overall, our results suggest that Red Bull might be a vulnerability factor to develop alcoholism given that it intensifies the consumption of higher concentrations of alcohol.

Telomere Length in Elite Athletes.

Growing evidence suggests that regular moderate-intensity physical activity is associated with an attenuation of leukocyte telomere length (LTL) shortening. However, more controversy exists regarding higher exercise loads such as those imposed by elite-sport participation. METHODS: The authors investigated LTL differences between young elite athletes (n = 61, 54% men, age [mean ± SD] 27.2 ± 4.9 y) and healthy nonsmoker, physically inactive controls (n = 64, 52% men, 28.9 ± 6.3 y) using analysis of variance (ANOVA). RESULTS: Elite athletes had, on average, higher LTL than control subjects, 0.89 ± 0.26 vs 0.78 ± 0.31, P = .013 for the group effect, with no significant sex (P = .995) or age effect (P = .114). CONCLUSIONS: The results suggest that young elite athletes have longer telomeres than their inactive peers. Further research might assess the LTL of elite athletes of varying ages compared with both age-matched active and inactive individuals.

A Paradox: α-Klotho Levels and Smoking Intensity.

Reports regarding smoking differences in α-klotho expression have provided conflicting results. In the current study we focused on the influence of smoking intensity to serum levels of the aging molecule α-klotho in healthy smokers. 40 middle aged healthy smokers without airway obstruction or restriction were selected for the analysis. Serum levels of soluble α-klotho were significantly higher in heavy smokers (P < 0.001). These results are in agreement with the possibility that α-klotho acts as anti-inflammatory molecule and strengthen the hypothesis that an increase of serum levels of α-klotho might be a compensatory response to smoking stress in healthy population.

Effect of Genetic Polymorphisms and Long-Term Tobacco Exposure on the Risk of Breast Cancer.

INTRODUCTION: Tobacco smoke contains many potentially harmful compounds that may act differently and at different stages in breast cancer development. The focus of this work was to assess the possible role of cigarette smoking (status, dose, duration or age at initiation) and polymorphisms in genes coding for enzymes involved in tobacco carcinogen metabolism (CYP1A1, CYP2A6) or in DNA repair (XRCC1, APEX1, XRCC3 and XPD) in breast cancer development. METHODS: We designed a case control study with 297 patients, 217 histologically verified breast cancers (141 smokers and 76 non-smokers) and 80 healthy smokers in a cohort of Spanish women. RESULTS: We found an association between smoking status and early age at diagnosis of breast cancer. Among smokers, invasive carcinoma subtype incidence increased with intensity and duration of smoking (all Ptrend < 0.05). When smokers were stratified by smoking duration, we only observed differences in long-term smokers, and the CYP1A1 Ile462Ile genotype was associated with increased risk of breast cancer (OR = 7.12 (1.98-25.59)). CONCLUSIONS: Our results support the main effect of CYP1A1 in estrogenic metabolism rather than in tobacco carcinogen activation in breast cancer patients and also confirmed the hypothesis that CYP1A1 Ile462Val, in association with long periods of active smoking, could be a breast cancer risk factor.

The Effect of Polymorphisms in DNA Repair Genes and Carcinogen Metabolizers on Leukocyte Telomere Length: A Cohort of Healthy Spanish Smokers.

INTRODUCTION: Smoking implies exposure to carcinogenic agents that causes DNA damage, which could be suspected to enhance telomere attrition. To protect and deal with DNA damage, cells possess mechanisms that repair and neutralize harmful substances. Polymorphisms altering DNA repair capacity or carcinogen metabolism may lead to synergistic effects with tobacco carcinogen-induced shorter telomere length independently of cancer interaction. The aim of this study was to explore the association between leukocyte telomere length (LTL) and several genetic polymorphisms in DNA repair genes and carcinogen metabolizers in a cohort of healthy smokers. METHODS: We evaluated the effect of six genetic polymorphisms in cytochrome P1A1 (Ile462Val), XRCC1 (Arg399Gln), APEX1 (Asp148Glu), XRCC3 (Thr241Met), and XPD (Asp312Asn; Lys751Gln) on LTL in a cohort of 145 healthy smokers in addition to smoking habits. RESULTS: Logistic regression analysis showed an association between XRCC1 399Gln allele and shorter telomere length (OR = 5.03, 95% CI = 1.08% to 23.36%). There were not association between the rest of polymorphisms analyzed and LTL. CONCLUSIONS: Continuous exposure to tobacco could overwhelm the DNA repair machinery, making the effect of the polymorphisms that reduce repair capacity more pronounced. Analyzing the function of smoking-induced DNA-repair genes and LTL is an important goal in order to identify therapeutic targets to treat smoking-induced diseases.

Are SNP-Smoking Association Studies Needed in Controls? DNA Repair Gene Polymorphisms and Smoking Intensity.

Variations in tobacco-related cancers, incidence and prevalence reflect differences in tobacco consumption in addition to genetic factors. Besides, genes related to lung cancer risk could be related to smoking behavior. Polymorphisms altering DNA repair capacity may lead to synergistic effects with tobacco carcinogen-induced lung cancer risk. Common problems in genetic association studies, such as presence of gene-by-environment (G x E) correlation in the population, may reduce the validity of these designs. The main purpose of this study was to evaluate the independence assumption for selected SNPs and smoking behaviour in a cohort of 320 healthy Spanish smokers. We found an association between the wild type alleles of XRCC3 Thr241Met or KLC3 Lys751Gln and greater smoking intensity (OR = 12.98, 95% CI = 2.86-58.82 and OR=16.90, 95% CI=2.09-142.8; respectively). Although preliminary, the results of our study provide evidence that genetic variations in DNA-repair genes may influence both smoking habits and the development of lung cancer. Population-specific G x E studies should be carried out when genetic and environmental factors interact to cause the disease.

Effects of cigarette smoking and nicotine metabolite ratio on leukocyte telomere length.

Studies of the effects of smoking on leukocyte telomere length (LTL) using cigarettes smoked per day or pack years smoked (PYS) present limitations. Reported high levels of smoking may not increase toxin exposure levels proportionally. Nicotine metabolism ratio (NMR) predicts total cigarette puff volume and overall exposure based on total N-nitrosamines, is highly reproducible and independent of time since the last cigarette. We hypothesized that smokers with higher NMRs will exhibit increased total puff volume, reflecting efforts to extract more nicotine from their cigarettes and increasing toxin exposure. In addition, higher levels of smoking could cause a gross damage in LTL. The urinary cotinine, 3-OH cotinine and nicotine levels of 147 smokers were analyzed using a LC/MS system Triple-Q6410. LTL and CYP2A6 genotype was determined by PCR in blood samples. We found a significant association between NMR and CYP2A6 genotype. Reduction in LTL was seen in relation to accumulated tobacco consumption and years smoking when we adjusted for age and gender. However, there were no significant differences between NMR values and LTL. In our study the higher exposure was associated with lower number of PYS. Smokers with reduced cigarette consumption may exhibit compensatory smoking behavior that results in no reduced tobacco toxin exposure. Our results suggest that lifetime accumulated smoking exposure could cause a gross damage in LTL rather than NMR or PYS. Nevertheless, a combination of smoking topography (NMR) and consumption (PYS) measures may provide useful information about smoking effects on health outcomes.