Evidence for gene-smoking interactions for hearing loss and deafness in Japanese American families

Background: This study investigated the relationship between smoking and hearing loss and deafness (HLD) and whether the relationship is modified by genetic variation. Data for these analyses was from the subset of Japanese American families collected as part of the American Diabetes Association Genetics of Non-insulin Dependent Diabetes Mellitus study. Logistic regression with generalized estimating equations assessed the relationship between HLD and smoking. Nonparametric linkage analysis identified genetic regions harboring HLD susceptibility genes and ordered subset analysis was used to identify regions showing evidence for gene-smoking interactions. Genetic variants within these candidate regions were then each tested for interaction with smoking using logistic regression models. Results: After adjusting for age, sex, diabetes status and smoking duration, for each pack of cigarettes smoked per day, risk of HLD increased 4.58 times (odds ratio (OR) = 4.58; 95% Confidence Interval (CI): (1.40,15.03)), and ever smokers were over 5 times more likely than nonsmokers to report HLD (OR = 5.22; 95% CI: (1.24, 22.03)). Suggestive evidence for linkage for HLD was observed in multiple genomic regions (Chromosomes 5p15, 8p23 and 17q21), and additional suggestive regions were identified when considering interactions with smoking status (Chromosomes 7p21, 11q23, 12q32, 15q26, and 20q13) and packs-per-day (Chromosome 8q21). Conclusions: To our knowledge this was the first report of possible gene-by-smoking interactions in HLD using family data. Additional work, including independent replication, is needed to understand the basis of these findings. HLD are important public health issues and understanding the contributions of genetic and environmental factors may inform public health messages and policies

Upstream stimulating factors: highly versatile stress-responsive transcription factors

International audienceUpstream stimulating factors (USF), USF-1 and USF-2, are members of the eucaryotic evolutionary conserved basic-Helix-Loop-Helix-Leucine Zipper transcription factor family. They interact with high affinity to cognate E-box regulatory elements (CANNTG), which are largely represented across the whole genome in eucaryotes. The ubiquitously expressed USF-transcription factors participate in distinct transcriptional processes, mediating recruitment of chromatin remodelling enzymes and interacting with co-activators and members of the transcription pre-initiation complex. Results obtained from both cell lines and knock-out mice indicates that USF factors are key regulators of a wide number of gene regulation networks, including the stress and immune responses, cell cycle and proliferation, lipid and glucid metabolism, and in melanocytes USF-1 has been implicated as a key UV-activated regulator of genes associated with pigmentation. This review will focus on general characteristics of the USF-transcription factors and their place in some regulatory networks