Cannabinoid Receptor 1 (<i>CNR1</i>) <i>4895 C/T</i> Genetic Polymorphism was Associated with Obesity in Japanese Men

Abstract

Aim:The aim of this study was to investigate the association of cannabinoid receptor 1 (CNR1) 4895 C/T gene polymorphism with obesity and obesity-related cardiovascular disease (CVD) risk factors in Japanese. Method: This study included 1,452 Japanese (678 men and 774 women, aged 25 to 74) from rural communities in Shimane Prefecture, Japan. Results: The frequency of the C minor allele of CNR1 4895 C/T polymorphism was 47%. In men, the CC genotype carriers showed significantly greater body mass index (BMI) and waist circumference (WC) values than T allele carriers, even after adjusting for age and medications for hypertension, dyslipidemia and type 2 diabetes. The frequency of obesity (BMI ≥ 25 kg/m 2 ) in CC genotype carriers was significantly greater than in T allele carriers (31.8% vs 21.5%), but the frequency of central obesity (WC ≥ 85 for men and WC ≥ 90 cm for women) was not significant by CNR1 4895 C/T genotype. CC genotype carriers of CNR1 4895 C/T showed, in logistic regression analysis, significantly greater odds for obesity than T allele carriers, even after adjustment for age and the abovementioned medications. Systolic blood pressure (SBP) values were also significantly different between the CC genotype and T allele carriers after controlling for age, medications for hypertension, dyslipidemia, and type 2 diabetes, and BMI or WC. Conclusion: This study supports the association of CNR1 4895 C/T with interindividual differences in obesity in men.

Genetic polymorphisms of the endocannabinoid system in obesity and diabetes

“…There may also be an impact of gender on these data. Male carriers of the mutant alleles of CNR1 polymorphisms rs1049353 and rs806368 have an increased likelihood of obesity . Similarly, the associations between the CNR2 polymorphism rs3123554 and lower BMI, weight and body fat percentage were reported in women .…”

“…However, negative associations were more common than positive associations (Figure ), suggesting that this SNP plays a part in a more complex genetic susceptibility to increased adiposity. Male carriers of the rs806368 mutant allele showed greater BMI values in a Japanese cohort ( P = 0.001) and were more likely to be obese ( P = 0.01; n = 1452) (Supporting Information Table S1).…”

“…Male carriers of the mutant alleles of CNR1 polymorphisms rs1049353 and rs806368 have an increased likelihood of obesity. 7,25 Similarly, the associations between the CNR2 polymorphism rs3123554 and lower BMI, weight and body fat percentage were reported in women. 40 Gender differences in feeding behaviour have been observed previously in animal models.…”

Cannabinoids in arterial, pulmonary and portal hypertension – mechanisms of action and potential therapeutic significance

“…Genetic studies have partly confirmed the potential involvement of eCBs in hypertension. Thus, in a study including 1452 adult Japanese, male, but not female, carriers of the CC genotype of base 4895 in the 3′ untranslated region of exon 4 of the cannabinoid CB 1 receptor gene (CNR1), are more likely to be obese and hypertensive than the TT or TC allele carriers (Mutombo et al ., ). By contrast, a large case–control study of 1968 individuals from Germany showed that 13 common single‐nucleotide polymorphisms in the cannabinoid CB 2 receptor gene (CNR2) were not significantly implicated in the development of classic cardiovascular risk factors including hypertension (Reinhard et al ., ).…”

Prevalence of lifestyle-related chronic diseases among agricultural and non-agricultural workers in ruralareas of Japan: the Shimane CoHRE study

“…Data on each participant's health status were obtained through a face-to-face interview, including questions regarding diagnosis and prescription medicines for diseases such as hypertension, dyslipidemia, diabetes, hyperuricemia, cerebrovascular disease, heart disease, nephropathy, hepatic disease, endocrine disease, and musculoskeletal disease. With regard to lifestyle habits, current smoking and the presence or absence of smoking history, and alcohol consumption were addressed 11) . A total of 102 individuals with missing variables were excluded from the study.…”