The Effect Of BRAP Gene Rs3782886and Environmental Factors And Their Interactions On Metabolic Syndrome

Backgrounds and ObjectivesMetabolic syndrome has gradually become a serious worldwide health problem. Although the prevalence of the metabolic syndrome in Chinese population is lower than in some developed countries, the number of metabolic syndrome patients increased rapidly in recent years. The ultimate threat of metabolic syndrome is that it leads to high risks of both type2diabetes and cardiovascular diseases and increases social health economic burden.As is known, metabolic syndrome is a complex disease which is caused by genetic factors, environmental factors and genetic-environmental interactions. In this study, a population based case-control study was conducted to examine the association between BRAP rs3782886locus and metabolic syndrome, and six environmental factors, smoking, alcohol consumption, physical activity, diet preference, sweet-food preferences and fried-food preferences were took into consideration in the association analysis with metabolic syndrome. Furthermore, genetic-environmental interactions were also considered to explore the causes of metabolic syndrome. The results can provide a theoretical basis for target population of surveillance and personalized intervention and prevention in Chinese.Materials and MethodsThe study was conducted based on a population case-control design and a total of4128subjects were recruited into the study, including1120cases,3008controls from seven regions:Beijing, Shanghai, Guangzhou, Hangzhou, Shenyang, Chengdu and Wenzhou. The candidate SNP rs3782886were genotyped from GWAS study, the first population validation, and the second population verification. GWAS study was used Illumina Human-OmniExpress-12vl.0chip technology. The first validation was used a technique of SNP Scan genotype. The second validation was genotyped on Taqman platform. The epidemiological data, including demographic characteristics, health status and dietary intake and behavior, were collected with a face to face interview by trained investigators. Anthropometric indices, including weight, height, waist circumference, systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured by trained physicians or investigators, following a standard protocol. Biochemical variables, including triglyceride (TG), high density lipoprotein (HDL), low density lipoprotein (LDL), and fasting plasma glucose (FPG) were measured using blood samples which were drawn after over12hours overnight fasting with a biochemical auto-analyzer (Hitachi7060, Tokyo, Japan). Continuous variables were expressed as means±standard deviations (SD) and categorical variables as frequencies (percentages). Statistical significances for continuous variables were assessed using Student’s t test and for categorical variables using Chi-square test. Hardy-Weinberg equilibrium tests were performed using Pearson’s Chi-square for the SNP among control subjects. The multiplicative interactions (MI) between SNPs and dietary behaviors were analyzed using logistic regression adding interaction terms. The additive interactions were analyzed departure from sum of effects as criterion of interaction and were quantified by ’Attributable Proportion due to Interaction, AP (95%CI). AP is the proportion of the incidence among individuals exposed to two interacting risk factors that is attributable to the interaction itself.ResultsIn the study, the effects of BRAP gene rs3782886and environmental factors and their interactions on metabolic syndrome were analyzed.(1) Association of BRAP rs3782886with metabolic syndromeT allele of BRAP rs3782886locus accounted for78.7%, C allele21.3%in cases of metabolic syndrome, and in controls T allele accounted for69.9%, C allele accounted for30.1%. The frequency of allele between the case and control groups were significantly different (P=3.23×10-15); The genotype of TT, TC, CC accounted for62.5%,32.3%,5.2%, respectively in the cases, and in the controls the TT, TC, CC genotype accounted for49.4%,41.1%,9.5%, respectively. The distributions of genotype in case and the control group was statistically significant difference (P=5.33×10-14). The mutant CC genotype decreased the risk of metabolic syndrome with the OR of TC genotype was0.59(95%CI=0.51-0.69), the OR=0.39(95%CI=0.29-0.53). After stratification by gender and adjustment of age, in male group, the OR of TC genotype was0.44(95%CI=0.36-0.55) and the OR of CC genotype was0.31(95%CI=0.20-0.47). In female group, the OR value of TC genotype was0.78(95%CI=0.63-0.97) and the OR value of CC genotype was0.50(95%CI=0.32-0.77). After stratification by age and adjustment of gender, in the group of less than45years old, the OR value of TC was0.43(95%CI=0.28-0.67) and the OR value of CC genotype was0.23(95%CI=0.08-0.67). In the group of more than45years old, the OR value of TC genotype was0.65(95%CI=0.55-0.76) and the OR value of CC genotype was0.43(95%CI=0.31-0.58).(2) Association of BRAP rs3782886with metabolic syndrome componentsAfter adjustment of age and gender, association was observed between BMI, blood pressure (SBP and DBP), TG, FPG and rs3782886(P<0.001). With increasing of the number of allele C, the average of these five metabolic syndrome components correspondingly increased. After adjusting for age, sex and BMI, DBP, HDLC, TG, FPG was found significant differences (P<0.01), the most significant statistically significant fasting blood glucose (P=6.56×10-10). SBP is mainly affected by the BMI, after adjustment for BMI was not statistically significant (P=0.512).(3) Association of environmental factors with metabolic syndromeIn the association analysis between environmental factors and metabolic syndrome, an increased risk of metabolic syndrome was respectively with drinking (OR=1.35,95%CI:1.15-1.58), middle physical activations (OR=1.39,95%CI:1.16-1.67) and low physical activations (OR=1.59,95%CI:1.33-1.90), meat diet preference (OR=1.6695%CI:1.40-1.97) and balanced diet preference (OR=1.34,95%CI:1.12-1.61), sweet-foods preference (OR=2.10,95%CI:1.82-2.43) and fried-foods preference (OR=1.24,95%CI:1.15-1.33). The factor of smoking had no association with metabolic syndrome (OR=1.15,95%CI:0.95-1.40, P=0.153).(4) Association of environmental factors with metabolic syndrome componentsFurther analysis of the relationship between environmental factors and metabolic syndrome components was conducted. After adjustment of age, gender and BMI, alcohol consumption had significant with BMI, HDLC and TG. Compared with the non-drinker group, BMI, HDLC and TG all increased (all P<0.0001). Physical activations were mainly associated with BMI, LDLC and HDLC. Medium, and low physical activities were risk factors with respect to high physical activity with statistically BMI, DBP increasing and HDLC decreasing (all P<0.05). Diet preferences along with the increase in the proportion of meat or fish, we can observe that BMI, LDL and FPG increased and the differences were statistically significant (P<0.0001). Sweet-food preference, the taste of sweets would significantly increase BMI, TG and FPG (All P<0.0001). Fried food preferences, the preferences of fried foods would increase BMI, DBP, TG and FPG and all the difference was statistically significant (all P<0.05).(5) The combined effects and interactions of BRAP rs3782886and environmental factorsIn the study we found BRAP rs3782886and environmental factors may exert joint effects on Chinese metabolic syndrome risk. We found that rs3782886mainly influenced drinking behaviors and distributions of sweet-foods preference (P=4.59×10-51and P=4.63×10-14). The results showed rs3782886had interaction with smoking, alcohol consumption, diet preference and physical activation. The rs3782886and smoking have multiplied and additive interaction, with the value of OR was1.22(95%CI=1.13-1.32) and AP (attributable proportion of interaction) was0.50(95%CI=0.36-0.64). The rs3782886and drinking have multiplied and additive interaction, with the value of OR was1.17(95%CI=1.09-1.27) and AP was0.43(95%CI=0.27-0.59), and the rs3782886and sweet-food preference have multiplied and additive interaction, with the value of OR was1.09(95%CI=1.01-1.18) and AP was0.38(95%CI=0.23-0.52). Also, the rs3782886and diet preference have multiplied and additive interaction, with the value of OR was1.07(95%CI=0.99-1.15) and AP was0.29(95%CI=0.12-0.45). Conclusions(1) Our study suggested that BRAP rs3782886was significantly associated with metabolic syndrome susceptibility and related metabolic components.(2) The environmental factors, including alcohol consumption, physical activation, diet preference, sweet-foods preference and fried-foods preferences were associated with the metabolic syndrome and related anthropometric indices and biochemical variables.(3) BRAP rs3782886associated with drinking behaviors and sweet-food preference. Compared with C allele, the carriers of T allele preferred to drink and sweet food.(4) There were genetic-environmental interactions between BRAP rs3782886and smoking, drinking, diet preference and sweet-foods preference. The TT genotype with the behaviors of smoking increased the risk of metabolic syndrome (OR=1.22,95%CI:1.13-1.32). The TT genotype with the behaviors of drinking increased the risk of metabolic syndrome (OR=1.17,95%CI:1.09-1.27). The TT genotype with the sweet-foods preference increased the risk of metabolic syndrome (OR=1.09,95%CI:1.01-1.18). The TT genotype with meat or fish preference increased the risk of metabolic syndrome (OR=1.07,95%CI:0.99-1.15).(5) The genetic susceptibility and environmental factors and their interaction played an important role on the metabolic syndromes.