Parental Smoking Modifies the Relation between Genetic Variation in Tumor Necrosis Factor-α (TNF) and Childhood Asthma

BACKGROUND: Polymorphisms in the proinflammatory cytokine genes tumor necrosis factor-α (TNF) and lymphotoxin-α (LTA, also called TNF-β) have been associated with asthma and atopy in some studies. Parental smoking is a consistent risk factor for childhood asthma. Secondhand smoke and ozone both stimulate TNF production. OBJECTIVES: Our goal was to investigate whether genetic variation in TNF and LTA is associated with asthma and atopy and whether the association is modified by parental smoking in a Mexican population with high ozone exposure. METHODS: We genotyped six tagging single nucleotide polymorphisms (SNPs) in TNF and LTA, including functional variants, in 596 nuclear families consisting of asthmatics 4–17 years of age and their parents in Mexico City. Atopy was determined by skin prick tests. RESULTS: The A allele of the TNF-308 SNP was associated with increased risk of asthma [relative risk (RR) = 1.54; 95% confidence interval (CI), 1.04–2.28], especially among children of non-smoking parents (RR = 2.06; 95% CI, 1.19–3.55; p for interaction = 0.09). Similarly, the A allele of the TNF-238 SNP was associated with increased asthma risk among children of nonsmoking parents (RR = 2.21; 95% CI, 1.14–4.30; p for interaction = 0.01). LTA SNPs were not associated with asthma. Haplotype analyses reflected the single SNP findings in magnitude and direction. TNF and LTA SNPs were not associated with the degree of atopy. CONCLUSIONS: Our results suggest that genetic variation in TNF may contribute to childhood asthma and that associations may be modified by parental smoking

Identification of Novel Single Nucleotide Polymorphisms in Inflammatory Genes as Risk Factors Associated with Trachomatous Trichiasis

infection, the primary cause of trachoma. Despite control programs that include mass antibiotic treatment, reinfection and recurrence of trachoma are common after treatment cessation. Furthermore, a subset of infected individuals develop inflammation and are at greater risk for developing the severe sequela of trachoma known as trachomatous trichiasis (TT). While there are a number of environmental and behavioral risk factors for trachoma, genetic factors that influence inflammation and TT risk remain ill defined. = 0.001] with the combination of TNFA (-308A), LTA (252A), VCAM1 (-1594C), SCYA 11 (23T) minor allele, and the combination of TNFA (-308A), IL9 (113M), IL1B (5′UTR-T), and VCAM1 (-1594C). However, TT risk increased 13.5 times [odds ratio = 13.5 (95% confidence interval 3.3–22), p = 0.001] with the combination of TNFA (-308G), VDR (intron G), IL4R (50V), and ICAM1 (56M) minor allele.Evaluating genetic risk factors for trachoma will advance our understanding of disease pathogenesis, and should be considered in the context of designing global control programs

We're in this Together: Sensation of the Host Cell Environment by Endosymbiotic Bacteria

Bacteria inhabit diverse environments, including the inside of eukaryotic cells. While a bacterial invader may initially act as a parasite or pathogen, a subsequent mutualistic relationship can emerge in which the endosymbiotic bacteria and their host share metabolites. While the environment of the host cell provides improved stability when compared to an extracellular environment, the endosymbiont population must still cope with changing conditions, including variable nutrient concentrations, the host cell cycle, host developmental programs, and host genetic variation. Furthermore, the eukaryotic host can deploy mechanisms actively preventing a bacterial return to a pathogenic state. Many endosymbionts are likely to use two-component systems (TCSs) to sense their surroundings, and expanded genomic studies of endosymbionts should reveal how TCSs may promote bacterial integration with a host cell. We suggest that studying TCS maintenance or loss may be informative about the evolutionary pathway taken toward endosymbiosis, or even toward endosymbiont-to-organelle conversion.Peer reviewe

Association of 77 polymorphisms in 52 candidate genes with blood pressure progression and incident hypertension : the Women's Genome Health Study

OBJECTIVE: Genetic risk factors for essential hypertension are largely unknown. The aim of the present study was to assess the association of 77 previously characterized gene variants in 52 candidate genes from various biological pathways with blood pressure (BP) progression and incident hypertension. METHODS: We analyzed data from 18 738 white women who participated in a prospective cohort study and were free of hypertension at baseline. BP progression at 48 months and incident hypertension during the entire follow-up according to the different genotypes were assessed by logistic regression and Cox proportional-hazards models, respectively. RESULTS: At 48 months of follow-up, 7889 of 16 635 women (47.4%) had BP progression. Only three of 70 polymorphisms with a minor allele frequency of at least 2% had a significant association with BP progression. The odds ratio [95% confidence interval (CI)] for 5,10-methylenetetrahydrofolate reductase (MTHFR) rs1801133 (minor allele T), natriuretic peptide precursor A (NPPA) rs5063 (minor allele A) and NPPA rs5065 (minor allele C) were 1.05 (1.00-1.10), 0.84 (0.76-0.94) and 0.93 (0.88-1.00), respectively. After adjustment for multiple testing using the false discovery rate, only the NPPA rs5063 association remained significant. During a median follow-up of 9.8 years, 5540 of 18 738 women developed incident hypertension. Only five of 70 polymorphisms were significantly associated with incident hypertension. The hazard ratio (95% CI) for interleukin 6 (IL-6) rs1800795 (minor allele C), MTHFR rs1801133, NPPA rs5063, nitric oxide synthase 3 rs1799983 (minor allele T) and transforming growth factor, beta 1 rs1800469 (minor allele T) were 0.96 (0.92-1.00), 1.06 (1.02-1.10), 0.88 (0.80-0.96), 1.05 (1.01-1.09) and 1.05 (1.01-1.10), respectively. After adjustment for multiple testing, none of these associations remained significant. CONCLUSION: NPPA gene polymorphisms may have a role in BP progression and incident hypertension. Our data also provide moderate confirmatory evidence of association between MTHFR rs1801133 and the development of hypertension