| Objective:Metabolic syndrome (MetS) is an aggregate which obesity, hypertension, high blood glucose and lipid metabolism disorders focus on, and its prevalence rate arrive to 20-25%. MetS is epidemic in the world and has become one of public health issues. The prevalence of MetS is rapidly increasing and contributes to social and economic burdens due to large population base our country. It is well known that the pathogenesis and etiology of MetS is related with genetic variations and circumstance. Recently, some researches suggested that PR domain-containing 16 (PRDM16) and Bone Mphogenetic Protein 7 (BMP7) may have significant impact on the regulation of energy expenditure and weight gain and were involved in the development of obesity, which is a key component of MetS. In addition, human BMP7 and PRDM16 map to chromosome 20ql3 and 1p3 respectively, susceptibility locus for obesity or MetS. Hence, BMP7 and PRDM 16 represent strong biological and positional candidates for susceptibility factors for obesity and Mets. Meanwhile, many studies showed that the prevalence of MetS in Xinjiang Uygur population is the higher than in other ethnic groups in China. Therefore, We systemically evaluated the association between variations of BMP7, PRDM16 and obesity or other phenotypes in the Chinese Uygur population by screening genetic variations of BMP7, PRDM16 in obesity patients, and genotyping their representative variations in the Uygur general population. Methods:The epidemiology investigation was performed during January to February 2007 among the Uygur population in the Hetian district in the Xinjiang Uygur Autonomous Region by cluster sampling and collected blood samples of 1371 Uygur subjects (male 582 and female 789). The diagnosis of metabolic syndrome based on the criteria of Internation diabetes federal. Total 1371 subjects were analyzed, including 672 MetS individuals and 699 non-MetS subjects. All exons, segmental introns and promoter regions of the BMP7, PRDM 16 gene were sequenced in 48 MetS Uygur Chinese subjects. Representative variations were selected according to the minor allele frequency (MAF) and linkage disequilibrium (LD). Representative variations were genotyped using the TaqMan polymerase chain reaction method in 672 patients and 699 non-obese controls. The distributions of patient characteristics, genotypes, or the allele frequency of SNPs between case and control groups were analyzed using the Student’s t-test or x2 analyses. All genotype distributions were tested for deviations from the Hardy-Weinberg equilibrium. Results:1) Epidemiology survey result showed:that the prevalence of MetS was high to 48%in Uygur population. The prevalence of abdominal obesity, hyperglycemia, hypertension and blood lipid disorders were 78%,57%,39%and 36% respectively. The prevalence of MetS is the highest prevalence of MetS was at 50-60 years olds and the prevalence of MetS in female population is more than in male population. The gender and drinking contributed to the development of MetS.2) Direct sequencing using DNA samples from 48 MetS patients identified 13 variations in the BMP7 gene. Five novel and 8 known variations in the BMP7 gene were identified. After considering their function, LD and MAF, among the identified genetic variations,3 SNPs were selected as representatives for genotyping experiments in the general population:-363>T (unsuccessfully genotyped) in 5’UTR,91398A>G in the introns, and 95694G>An in 3’UTR. Direct sequencing using DNA samples from 48 MetS patients identified 43 variations in the PRDM16 gene.17 novel and 26 known variations in the PRDM 16 gene were identified. After considering their function, LD and MAF, among the identified genetic variations,4 SNPs were selected as representatives for genotyping experiments in the general population:315898T>C and 342836C>T in extrons,356981G>T in the introns, and 367039T>G in 3’UTR.3) The genotype distributions of each SNP in general population, MetS and non-MetS population were tested and all of them conform Hardy-Weinberg equilibrium (HWE P> 0.05). The distributions of the genotypes (dominant model) of 4 SNPs in PRDM16 gene did not differ between the MetS and non-MetS groups. The distributions of the genotypes (additive model) for rs6025422 of BMP7 gene differed significantly between MetS and non-MetS groups and the statistic power is 0.914. Haplotype based association study in Xinjiang Uygur population showed that frequence of (C-G-C-G) H3 and (C-G-T-G) H4 in nor-MetS population were different from ones in MetS population.4) The studies of association between BMP7 gene and disease which were components of MetS showed:The distributions of the genotypes (additive model) for rs6025422 of BMP7 differed significantly between obese and non-obese groups and WC and BMI were significantly associated with the genotypes of rs6025422, and that GG genotype is protective factor. The rs6025422 of BMP7 was associated with diabetes and fast blood glucose, fast insulin and HOMA-index were significantly different between different genotypes of rs6025422 in male Uygur population. There were significant differences of genotype distribution of rsl7480735 between hypertension and control groups (P<0.05). And the means of blood pressure significantly different in individuals with GG, GA+AA genotypes of rs17480735 in individuals with age≥50 years (P<0.05). The logistic regression analysis showed that AA genotype of rs17480735 variation might be a hypertension risk factor in individual with age≥50years (OR=1.445,95%CI 1.031-1.626, P=0.017). There were significant differences of genotype distribution of rs6025422 between Hypertriglyceridemia and control groups (P=0.001). And the levels of triglyceride (TG) significantly decreased in individuals with AA, AG and GG genotypes of rs60254222 (.P=0.001). Odd ratio (OR) value adjusted for age, gender, BMI, smoking and drinking was 0.562 by logistic regression analysis (95%CI 0.393-0.802,.P=0.002). Conclusion:The prevalence of MetS and abdominal obesity obesity, hyperglycemia, hypertension and blood lipid disorders were higher in Xinjiang Uygur population. The prevalence of MetS is the highest in 50-60 years older and the prevalence of MetS in female is significantly higher than in male population. The variations in the BMP7 gene were associated with MetS and hypertension, Hypertriglyceridemia, diabetes which were components of MetS in Uygur Chinese population. The haplotype of PRDM16 gene was associated with MetS in Uygur Chinese population. |
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