Association Study Of Liver X Receptor β Polymorphism And Metabolic Syndrome In Chinese Han Population

Object:To investigate the relationship between rs2695121 polymorphism of LXRβ and the susceptibility to metabolic syndrome and its related components in Chinese Han population. If one susceptible gene of metabolic syndrome is determined, our research can offer a reliable theory to predict people with high risk of suffering metabolic syndrome and supply an early intervention.Methods:1. A total of 624 Chinese Han participants (aged from 40-65 years old) were recruited from Caihe community, Hangzhou City, Zhejiang Province in 2011, into this study. The Ethics Committee of Sir Run Run Shaw Hospital approved the study protocol. During the 2-year follow-up period (2013),160 participants dropped out. At the end of the study,464 participants were followed up,178 males and 286 females. All cases diagnosed with Mets were based on the Joint Commit-tee for Developing Chinese Guidelines on Prevention and Treatment of Dyslipidemia in Adults (JCDCG) (2007). The sample comprises 85 individuals (48 males and 37 females) with metabolic syndrome (MetS) and 379 individuals (130 males and 249 females) without metabolic syndrome (non-MetS). Our research measured the general information, such as age, gender, life style, past history. Meanwhile, we also measured the waist circumference, hip circumference, waist/hip ratio, visceral fat area (VFA), subcutaneous fat area (SFA), systolic blood pressure (SBP), diastolic blood pressure (DBP), fast plasma glucose (FPG)& 2h plasma glucose, fast insulin (FINS)& 2h insulin, total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), glycosylated hemoglobin, blood uric acid (BUA), serum creatinine (SCr), blood urea nitrogen (BUN) and so on. We then followed up these participants for 2 years.2. Genotyping was tested by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP).3. The genotype distribution in MetS group and non-MetS group were test on the Hardy-Weinberg equilibrium. The frequency of the genotypes and alleles of rs2695121 were compared between groups by chi square test. We also analyzed clinical data, MetS and MetS associated compositions relation with this gene polymorphism, the baseline of new onset MetS and non-onset MetS after 2 years follow-up. These datas were calculatied by t test or Wilcoxon test based on K-S test. Also, we calculated the risk factors of MetS and new-onset MetS by using binary regression method.Results:1. Participants common clinical materials:No matter male or female, MetS group had a significant higher (P<0.05) in weight, BMI, waist circumference, hip circumference, waist/hip ratio, VFA, SBP, DBP, FPG & 2h plasma glucose, FINS & 2h insulin, glycosylated hemoglobin, HOMA-IR, TG, BUA, MALB/CR, ALT, y-GT while a significant lower (P<0.05) in HDL-C, comparing with non-MetS. Meanwhile, MetS group had a higher SFA and TC only in male (P<0.05).2.Genetic equilibrium text:The genotype distributions in both non-MetS group (P=0.173) and MetS group (P=0.689) were in Hard-Weinberg equilibrium, indicating the genotype distribution in each group was in the Hardy-Weinberg equilibrium.3. Genotypes and alleles of rs2695121 polymorphism:Among the Chines Han population in Caihe Community, Hangzhou City, Zhejiang Province, we found there were 3 genotypes of rs2695121:CC, CT, TT. Among the whole participants, the percentage of genotypes (CC, CT, TT) were 62.4%,34.1%,3.5% in MetS group and 73.6%,25.3%,1.1% in non-MetS group, respectively. The C allele and T allele were each found in 79.4%,20.6% of MetS and 86.3%,13.7%of non-MetS. Neither the genotypes nor alleles frequencies suggested a difference in distribution (P=0.121, P=0.132). Apart participants with gender, we found that 50.0%,43.7%,6.3% in MetS group and 70.8%,28.5%,0.7% in non-MetS group according to genotypes in males. C and T alleles were 71.9%,28.1% and 85.0%,15.0%, respectively, also sharing significant difference in distribution in both genotype and allele (P=0.006, P=0.019). However, in female group, we found there were no significant difference in distribution in neither genotype nor allele(0.564, P=0.414) based on the result of 78.4%,21.6%, 0.0% in MetS group and 75.1%,23.7%,1.2% in non-MetS while 89.2%,10.8% and 86.9%,13.1% in C, T alleles, respectively. Based on the MetS each diagnosis criteria cutoff, we set apart the participants into two groups, respectively,abdominal obesity group and non-abdominal obesity group, hyperglycemia group and normal blood glucose group, hypertension group and normal blood pressure group, high triglyceride group and normal triglyceride group, low HDL-C group and normal HDL-C group. We found there was no significant difference in both genotype and allele of all the subgroup.4. rs2695121 polymorphism and general clinical materials:Compare with CC group, the mutant T group had a higher BMI (P=0.007), waist circumference (P=0.004), BUA (P=0.001) in male, while there were no difference in female.5. rs2695121 polymorphism and metabolic syndrome:We found out that compared with the CC group, CT+TT group was nominally associated with an increased risk of MetS in male (OR= 2.421,95% CI 1.226-4.781, P= 0.010) but female group still showed no significant (OR= 0.832,95%CI 0.361-1.915, P= 0.665).6. Other components and metabolic syndrome:No matter in male or in female, we found that BMI、SFA and BUA except MetS dignosed criterias were strongly related to metabolic syndrome. In the binary logistics analysis, we found that higher BUA (OR-2.050,95%CI 1.354-3.102, P=0.001) suggested a higher risk of MetS in female.7. New onset MetS risk analysis after 2 years follow-up:In male, non-MetS paricipants with higher waist circumference, TG and lower HDL-C might easily develop into MetS in 2 years. In female, non-MetS paricipants with higher BMI, obvious abdominal obesity, hypertension, hyperglycemia, hyperinsulinemia, higher HOMA-IR and dyslipidemia might easily develop into MetS in 2 years. In the binary logistics analysis, we found no index could suggest a significant higher or lower risk of MetS.Conclusion:1. The polymorphism of rs2695121 in Chinese Han population in Caihe Community, Hangzhou City, Zhejiang Province. Both genotype and allele of rs2695121 had a dominant distribution in male but not in female when comparing between MetS group and non-MetS group.2. The polymorphism of rs2695121 might relate to MetS occurrence. Carrying mutant T allele could increase risk of metabolic syndrome only in male but not in female,.3. In male, above the baseline of waist circumference, triglyceride or under the baseline of HDL-C might easily developmed into MetS while in female, having central obese, insulin resistence and dyslipidemia might suggest a trend of developing into MetS. However, rs2695121 might have no infruence on new onset MetS.