Determination of genetic correlation between tobacco smoking and coronary artery disease.

Backgrounds: Tobacco smoking is an important risk factor for coronary artery disease (CAD), but the genetic mechanisms linking smoking to CAD remain largely unknown. Methods: We analyzed summary data from the genome-wide association study (GWAS) of the UK Biobank for CAD, plasma lipid concentrations (n = 184,305), and smoking (n = 337,030) using different biostatistical methods, which included LD score regression and Mendelian randomization (MR). Results: We identified SNPs shared by CAD and at least one smoking behavior, the genes where these SNPs are located were found to be significantly enriched in the processes related to lipoprotein metabolic, chylomicron-mediated lipid transport, lipid digestion, mobilization, and transport. The MR analysis revealed a positive correlation between smoking cessation and decreased risk for CAD when smoking cessation was considered as exposure (p = 0.001), and a negative correlation between the increased risk for CAD and smoking cessation when CAD was considered as exposure (p = 2.95E-08). This analysis further indicated that genetic liability for smoking cessation increased the risk of CAD. Conclusion: These findings inform the concomitant conditions of CAD and smoking and support the idea that genetic liabilities for smoking behaviors are strongly associated with the risk of CAD.

Mendelian randomization analyses of smoking and Alzheimer's disease in Chinese and Japanese populations.

Background: Previous epidemiological studies have reported controversial results on the relationship between smoking and Alzheimer's disease (AD). Therefore, we sought to assess the association using Mendelian randomization (MR) analysis. Methods: We used single nucleotide polymorphisms (SNPs) associated with smoking quantity (cigarettes per day, CPD) from genome-wide association studies (GWAS) of Japanese population as instrumental variables, then we performed two-sample MR analysis to investigate the association between smoking and AD in a Chinese cohort (1,000 AD cases and 500 controls) and a Japanese cohort (3,962 AD cases and 4,074 controls), respectively. Results: Genetically higher smoking quantity showed no statistical causal association with AD risk (the inverse variance weighted (IVW) estimate in the Chinese cohort: odds ratio (OR) = 0.510, 95% confidence interval (CI) = 0.149-1.744, p = 0.284; IVW estimate in the Japanese cohort: OR = 1.170, 95% confidence interval CI = 0.790-1.734, p = 0.434). Conclusion: This MR study, for the first time in Chinese and Japanese populations, found no significant association between smoking and AD.

Genetic variations in the bitter taste receptor gene TAS2R38 are related to cigarette smoking behavior in Han Chinese smokers.

BACKGROUND: Smoking behavior is influenced by multiple genes, including the bitter taste gene TAS2R38. It has been reported that the correlation between TAS2R38 and smoking behavior has ethnicity-based differences. However, the TAS2R38 status in Chinese smokers is still unclear. OBJECTIVE: This study aims to investigate the possible relationship between genetic variations in TAS2R38 (A49P, V262A and I296V) and smoking behaviors in the Han Chinese population. METHODS: The haplotype analyses were performed and smoking behavior questionnaire was completed by 1271 individuals. Genetic association analyses for smoking behavior were analyzed using chi-square test. Further, for investigating the molecular mechanism of TAS2R38 variants effect on smoking behavior, we conducted TAS2R38-PAV and TAS2R38-AVI expression plasmids and tested the cellular calcium assay by cigarette smoke compounds stimulus in HEK293. RESULTS: Significant associations of genetic variants within TAS2R38 were identified with smoking behavior. We found a higher PAV/PAV frequency than AVI/AVI in moderate and high nicotine dependence (FTND ≥ 4; X2 = 4.611, 1 df, p = 0.032) and strong cigarette smoke flavor intensity preference (X2 = 4.5383, 1 df, p = 0.033) in participants. Furthermore, in the in vitro cellular calcium assay, total particle matter (TPM), N-formylnornicotine and cotinine, existing in cigarette smoke, activated TAS2R38-PAV but not TAS2R38-AVI-transfected cells. CONCLUSION: Our data highlights that genetic variations in TAS2R38 are related to smoking behavior, especially nicotine dependence and cigarette smoke flavor intensity preference. Our findings may encourage further consideration of the taste process to identify individuals susceptible to nicotine dependence, particularly Han Chinese smokers.

Nutrigenomics reveals potential genetic underpinning of diverse taste preference of Chinese men.

BACKGROUND: Taste preference varies geographically in China. However, studies on Chinese people's taste preference in different regions of China are limited, and are lack of research on the mechanism of differences in taste preference, especially in genetics. OBJECTIVE: This study aims to investigate the characteristics of taste preference of Chinese men, and estimate whether diverse taste preference in Chinese have genetic underpinning. METHODS: We conducted a questionnaire survey on taste preferences on 1076 males from 10 regions of China, and collected another 1427 males from the same regions which genotyped by microarray. We compared the correlation between different taste preference, and evaluated the correlation between the mutation frequency of inhouse database and different taste preference. The putative taste-preference-related genes were further utilized to estimate the candidate relationship on gene and gene network in different taste preference. RESULTS: There was a correlation between different taste preferences in Chinese men. We found 31 SNPs associated with 6 kind of taste preferences. These SNPs located within or nearby 36 genes, and the tastes associated with 4 of these genes (TRPV1, AGT, ASIC2 and GLP1R) are consistent with the previous studies. Moreover, in different tastes which were suggested to be associated with each other, some putative related genes were the same or in the same gene network, such as pathways related with blood pressure, response to stimulus and nervous system. CONCLUSIONS: This study indicates that the diverse taste preference of Chinese men may have genetic underpinning.

Genome-Wide Association Study of Smoking Behavior Traits in a Chinese Han Population.

Tobacco use is one of the leading causes of preventable disease worldwide. Genetic studies have elucidated numerous smoking-associated risk loci in American and European populations. However, genetic determinants for cigarette smoking in Chinese populations are under investigated. In this study, a whole-genome sequencing (WGS)-based genome-wide association study (GWAS) was performed in a Chinese Han population comprising 620 smokers and 564 nonsmokers. Thirteen single-nucleotide polymorphisms (SNPs) of the raftlin lipid linker 1 (RFTN1) gene achieved genome-wide significance levels (P < 5 x 10-8) for smoking initiation. The rs139753473 from RFTN1 and six other suggestively significant loci from CUB and sushi multiple domains 1 (CSMD1) gene were also associated with cigarettes per day (CPD) in an independent Chinese sample consisting of 1,329 subjects (805 smokers and 524 nonsmokers). When treating males separately, associations between smoking initiation and PCAT5/ANKRD30A, two genes involved in cancer development, were identified and replicated. Within RFTN1, two haplotypes (i.e., C-A-C-G and A-G-T-C) formed by rs796812630-rs796584733-rs796349027-rs879511366 and three haplotypes (i.e., T-T-C-C-C, T-T-A-T-T, and C-A-A-T-T) formed by rs879401109-rs879453873-rs75180423-rs541378415-rs796757175 were strongly associated with smoking initiation. In addition, we also revealed two haplotypes (i.e., C-A-G-G and T-C-T-T derived from rs4875371-rs4875372-rs17070935-rs11991366) in the CSMD1 gene showing a significant association with smoking initiation. Further bioinformatics functional assessment suggested that RFTN1 may participate in smoking behavior through modulating immune responses or interactions with the glucocorticoid receptor alpha and the androgen receptor. Together, our results may help understand the mechanisms underlying smoking behavior in the Chinese Han population.

Four-week administration of nicotinemoderately impacts blood metabolic profile and gut microbiota in a diet-dependent manner.

As the primary active component in tobacco, nicotine affects many aspects of human metabolism. Diet and gut microbiota are key factors that profoundly influence human lipid and glucose metabolism. However, the diet-based differential impacts of nicotine on blood lipid and glucose levels as well as on the gut microbiota are still largely unknown. Here we show that 4-week oral administration of nicotine (2 mg/kg) resulted in bodyweight and fat decrease in both normal-chow (NCD)- and high-fat diet (HFD)-fed mice. But nicotine showed little influence on the plasma levels of lipids, glucose and inflammatory cytokines in NCD-fed mice but moderately deteriorated these parameters in HFD-fed ones. 16S sequencing showed that nicotine perturbed bacterial diversity and community composition of gut microbiota more pronouncedly in HFD mice. At genus level, nicotine dramatically increased Ruminococcaceae UCG-009 in HFD condition but not in NCD feeding. Interestingly, co-treatment with antibiotics (ampicillin + norfloxacin) substantially abolished the lipid-enhancing effect of nicotine in HFD-fed mice, suggesting an important role of gut microbes in the lipid-modulatory effect of nicotine. Together, our results indicate that the harmful effects of nicotine on metabolism and systemic inflammation are diet-dependent. Chronic exposure to nicotine may alter the gut microbiota especially in HFD-fed animals.

[Analysis of volatile components in Qingshanlvshui tea using solid-phase microextraction/accelerated solvent extraction-gas chromatography-mass spectrometry].

The volatile components of Qingshanlvshui Tea were extracted using solid phase micro-extraction (SPME) and accelerated solvent extraction (ASE), and then were identified by gas chromatography-mass spectrometry (GC-MS). It showed that ninety-one compounds were identified, including forty-nine by SPME, fifty-six by ASE, and fourteen by both of them. The main constituents were beta-myrcene, 3,5,5-trimethyl-1,5-heptadiene, L-limonene, alpha-ocimene, beta-ocimene, beta-pinene, 2-methylbenzaldehyde, 5-(hydroxymethyl)-2-furfural. Both SPME and ASE have their advantages. SPME is excellent at simplicity, rapidity, solvent-free, high enrichment, low detection limit, environment friendly etc. ASE has characteristics of time and solvent saving, automation, simplicity, as well as high efficiency.