Association between habitual coffee consumption and skeletal muscle mass in middle-aged and older Japanese people.

AIMS: Coffee consumption has been suggested, in animal studies, to inhibit the progression of sarcopenia, possibly through its anti-inflammatory effects; however, few studies have been carried out in humans. We aimed to examine whether coffee consumption was related to indicators of sarcopenia in a Japanese population, and whether the association was mediated by reduced inflammation. METHODS: This study was a cross-sectional design. Participants were community residents (n = 6369) aged 45-74 years. We measured skeletal muscle mass index (SMI; kg/m2 ) by a bioelectrical impedance method, and grip strength with a Smedley-type dynamometer. Habitual coffee consumption was assessed by a self-administered questionnaire. Serum high-sensitivity C-reactive protein was measured as an inflammatory marker. The association between habitual coffee consumption and SMI or grip strength was analyzed with a linear regression model adjusted for covariates. RESULTS: A significant positive association was found between coffee consumption and SMI (men: ß = 0.023; Ptrend  = 0.004, women: ß = 0.011; Ptrend  = 0.012). Further adjustment for high-sensitivity C-reactive protein did not materially alter the results (men: ß = 0.023; Ptrend  = 0.005, women: ß = 0.009; Ptrend  = 0.024). The relationship between coffee consumption and grip strength did not reach statistical significance; however, a positive trend was observed (men: ß = 0.208; Ptrend  = 0.085, women: ß = 0.092; Ptrend  = 0.167). CONCLUSIONS: We found that coffee consumption was positively associated with SMI independently of inflammation in middle-aged and older Japanese people. Reduced inflammation by coffee does not seem to be an important mediator, and further investigations are required to explore the mechanisms of this association. Geriatr Gerontol Int 2021; 21: 950-958.

Genome-wide association meta-analysis and Mendelian randomization analysis confirm the influence of ALDH2 on sleep durationin the Japanese population.

Usual sleep duration has substantial heritability and is associated with various physical and psychiatric conditions as well as mortality. However, for its genetic locus, only PAX8 and VRK2 have been replicated in previous genome-wide association studies (GWAS). We conducted a GWAS meta-analysis of self-reported usual sleep duration using three population-based cohorts totaling 31 230 Japanese individuals. A genome-wide significant locus was identified at 12q24 (p-value < 5.0 × 10-8). Subsequently, a functional variant in the ALDH2 locus, rs671, was replicated in an independent sample of 5140 Japanese individuals (p-value = 0.004). The association signal, however, disappeared after adjusting for alcohol consumption, indicating the possibility that the rs671 genotype modifies sleep duration via alcohol consumption. This hypothesis explained a modest genetic correlation observed between sleep duration and alcohol consumption (rG = 0.23). A Mendelian randomization analysis using rs671 and other variants as instrumental variables confirmed this by showing a causal effect of alcohol consumption, but not of coffee consumption on sleep duration. Another genome-wide significant locus was identified at 5q33 after adjusting for drinking frequency. However, this locus was not replicated, nor was the PAX8 and VRK2. Our study has confirmed that a functional ALDH2 variant, rs671, most strongly influences on usual sleep duration possibly via alcohol consumption in the Japanese population, and presumably in East Asian populations. This highlights the importance of considering the involvement of alcohol consumption in future GWAS of usual sleep duration, even in non-East Asian populations, where rs671 is monomorphic.

A genome-wide association study in the Japanese population identifies the 12q24 locus for habitual coffee consumption: The J-MICC Study.

Coffee is one of the most widely consumed beverages worldwide, and its role in human health has received much attention. Although genome-wide association studies (GWASs) have investigated genetic variants associated with coffee consumption in European populations, no such study has yet been conducted in an Asian population. Here, we conducted a GWAS to identify common genetic variations that affected coffee consumption in a Japanese population of 11,261 participants recruited as a part of the Japan Multi-Institutional Collaborative Cohort (J-MICC) study. Coffee consumption was collected using a self-administered questionnaire, and converted from categories to cups/day. In the discovery stage (n = 6,312), we found 2 independent loci (12q24.12-13 and 5q33.3) that met suggestive significance (P < 1 × 10-6). In the replication stage (n = 4,949), the lead variant for the 12q24.12-13 locus (rs2074356) was significantly associated with habitual coffee consumption (P = 2.2 × 10-6), whereas the lead variant for the 5q33.3 locus (rs1957553) was not (P = 0.53). A meta-analysis of the discovery and replication populations, and the combined analysis using all subjects, revealed that rs2074356 achieved genome-wide significance (P = 2.2 × 10-16 for a meta-analysis). These findings indicate that the 12q24.12-13 locus is associated with coffee consumption among a Japanese population.

Macronutrient intakes and serum oestrogen, and interaction with polymorphisms in CYP19A1 and HSD17B1 genes: a cross-sectional study in postmenopausal Japanese women.

Although higher circulating levels of oestrogen are related to postmenopausal breast cancer risk, limited information is available regarding effects of diet on endogenous oestrogen. Thus, we examined associations between macronutrient intakes and serum oestrogen with consideration of polymorphisms in oestrogen-metabolising genes. In this cross-sectional study, 784 naturally menopaused Japanese women aged 47-69 years were selected from participants of the Japan Multi-Institutional Collaborative Cohort Study. We documented dietary intakes, measured serum concentrations of oestrone (E1) and oestradiol (E2) and genotyped polymorphisms in oestrogen-metabolising CYP19A1 (rs4441215 and rs936306) and HSD17B1 (rs605059) genes. Trends and interactions were examined using linear regression models. In addition, we calculated the ratios of the oestrogen concentrations of the second to the highest quartiles (Q2-Q4) of dietary intake to those of the lowest quartiles (Q1). After adjustment for potential confounders, E2 was significantly associated with intake of carbohydrate and noodles; ratios of Q4 v. Q1 were 1·15 (95 % CI 1·04, 1·28) and 1·15 (95 % CI 1·04, 1·26), respectively. In contrast, E2 levels were inversely associated with intake of total energy, SFA and n-3 highly unsaturated fatty acids (n-3 HUFA); ratios of Q4 v. Q1 were 0·90 (95 % CI 0·82, 0·99), 0·89 (95 % CI 0·81, 0·98) and 0·91 (95 % CI 0·83, 1·00), respectively. In stratified analysis by polymorphisms, the rs605059 genotype of HSD17B1 significantly modified associations of E2 with intake of n-3 HUFA and fish; the associations were limited to those with the CC genotype. Macronutrient intakes were associated with serum E2 level, and these associations may be modified by HSD17B1 polymorphism in postmenopausal women.

Regulation of hypothalamic gene expression by glucocorticoid: implications for energy homeostasis.

The present study investigated the hypothalamic gene expressions regulated by glucocorticoids (GC), key hormones in energy homeostasis. Using the serial analysis of gene expression (SAGE) method, we studied the effects of adrenalectomy (ADX) and GC on the transcriptomes of mouse hypothalamus. Approximately 180,000 SAGE tags, which correspond to 50,000 tag species, were isolated from each group of intact or adrenalectomized mice as well as 1, 3, and 24 h after GC injection. ADX upregulated diazepam binding inhibitor gene expression while downregulating vomeronasal 1 receptor D4, genes involved in mitochondrial phosphorylation (cytochrome-c oxidase 1 and NADH dehydrogenase 3), 3beta-hydroxysteroid dehydrogenase-1, and prostaglandin D2 synthase. GC increased the gene expression levels of dehydrogenase/reductase member 3, prostaglandin D2 synthase, solute carrier family 4 member 4, and five cytoskeletal proteins including myosin light chain phosphorylatable fast and troponin C2 fast. On the other hand, GC reduced the mRNA levels of calmodulin 1 and expressed sequence tag similar to calmodulin 2, ATP synthase F0 subunit 6, and solute carrier family 4 member 3. Moreover, 7 uncharacterized and 43 novel transcripts were modulated by ADX and GC. The present study has identified genes that may regulate hypothalamic systems governing energy balance in response to ADX and GC.

The top 10 most abundant transcripts are sufficient to characterize the organs functional specificity: evidences from the cortex, hypothalamus and pituitary gland.

Using serial analysis of gene expression, we have identified the most abundant mRNA transcripts in parietal cortex, hypothalamus and pituitary gland in adult male mice. High mRNA abundance of neurogranin (cell signalling and communication) was characteristic of the cortex. The common molecular features of cortex and hypothalamus were high abundance of mRNA encoding mitochondrial enzymes such as reduced form of nicotinamide adenine dehydrogenase (NADH) 4 and cytochrome c oxidase 2 (energy metabolism), brain creatine kinase (energy metabolism) and myelin basic protein (cell structure). In the hypothalamus, mRNA levels of apolipoprotein E (lipid metabolism), prostaglandin D2 (cell signalling and communication) and secreted acidic cysteine-rich glycoprotein (extracellular matrix) were especially high. A common molecular feature of the hypothalamus and pituitary was high mRNA abundance of guanine nucleotide binding protein alpha stimulating complex locus (cell signalling and cell communication). The pituitary gland was characterized by high expression of genes encoding hormones such as growth hormone, pro-opiomelanocortin and prolactin, as well as neuronatin (cell differentiation) and four potential novel transcripts. Thus, these results show that the cortex, hypothalamus and pituitary gland can be specifically characterized according to their 10 most abundant transcripts. In addition, the current study serves as a basis for future studies on the potential novel transcripts and the transcripts with unclear functions despite their extremely high abundance, as well as studies on physiology and pathology of the two brain regions and pituitary gland.