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Study On The Body Mass Index Reference Norm, The Assoication Between PLIN Gene Polymorphisms And Obesity And Response To Anti-obesity Intervention In Uygur And Han Population Aged 7~18

Posted on:2010-08-13Degree:DoctorType:Dissertation
Country:ChinaCandidate:J H DaiFull Text:PDF
GTID:1114360305990290Subject:Occupational and Environmental Health
Abstract/Summary:PDF Full Text Request
Objective:The worldwide epidemic of childhood obesity is an emerging global public health challenge. Obesity is not only an unhealthy state, but also associated with an increased risk of type 2 diabetes mellitus, heart disease, metabolic syndrome, hypertension, stroke, and certain forms of cancer. Body mass index (BMI; in kg/m2) has achieved international acceptance as a standard for the screening of overweight and obesity. It is closely related to body fat content, long-term health effects and the risk of disease. It has the advantages of simply calculated, easily measured, low-cost and reproducibility. It is widely adopted and applied in the population screening, large-scale epidemiological investigation and assessment of obesity. Children and adolescents are in a period of rapid growth and development, so it is needed to be used the BMI reference norm for defining overweight and obesity according to different ages and genders. Due to different races or ethnic groups, obesity-related diseases have difference between the risk of occurrence and death on the same BMI level, the BMI reference norm is ethnically different. Uygur, the main ethnicity in Xinjiang, has different genetic background, living habits and dietary pattern with Han ethnicity, which are closely related to the occurrence of obesity. It is necessary to establish the BMI reference norm for defining overweight and obesity in different ethnic children and adolescents in the same area. The causes of obesity are complex. The study of mechanism of obesity has reached the level of gene regulation. Perilipin, encoded by the gene PLIN, is an important protein in the regulation of fat metabolism pathway. A number of studies showed that PLIN gene closely related to the occurrence of obesity, and has population specificity. However, it has not previously been reported that PLIN gene is associated with the obesity in Uygur people. The purpose of this study is to investigate whether PLIN gene polymorphisms were associated with obesity and obesity-related changes with and without intervention in school-age children and adolescents with Uygur and Han ethnic backgrounds in Urumqi. The association study of the gene and the effect of intervention, provide a theoretical evidence for drawing up individualized programs of obesity intervention. Methods:1)A total number of 9146 boys and girls in Urumqi, Xinjiang, aged 7~18 years, were recruited by stratifying and clustering sampling from April to June 2004. Using the internationalλmedian coefficient of variation method in the development of overweight children obese reference by the International Obesity Working Group (International Obesity Task Force, IOTF), BMI centile curves with 7~18 age were drawn according to gender and ethnicity. Using LMS software (Tim cole and Huiqi Pan) which were making the centile curves passing through 25kg/m2 and 30kg/m2 (International Obesity Task Force, IOTF), and 24kg/m2 and 28kg/m2 (Work Group on Obesity in China, WGOC) at age of 18 for overweight and obesity respectively, the age and sex specific BMI cutoff points for children with Uygur and Han ethnicities were constructed.2) Based on the obese group screened by the cross-sectional investigation, a group-matched case-control study was carried out. We examined four types of tag single nucleotide polymorphisms (SNPs) at the perilipin (PLIN) locus (rs1052700A/T (SNP1), rs8179043A/G (SNP2), rs6496589C/G (SNP3) and rs4578621C/G (SNP4)) to investigate their association with obesity risk. The study population included 616 subjects of Uygur and Han ethnic children and adolescents in Urumqi. Moreover, by following-up the study subjects for a year, we observed the change of obesity state of subjects under the natural growth and development conditions and tried to analyze the association between PLIN gene polymorphisms and obesity, obesity-related phenotypes and the change of obesity state.3) Adopted two major measures of peer education-based health education and 50 minutes physical activity 3 times a week,364 Uygur and Han ethnic school-aged children aged 7-11 years were divided into three groups, namely control group, the first intervention group (simple health education group) and the second intervention group (health education plus physical activity). In three primary schools, a 7 month-period obesity intervention trial was conducted and the effects of obesity intervention were evaluated. At the same time, the association between PLIN gene polymorphisms and intervention effect was studied. Results:1) The age and sex specific BMI centile curves were drawn for children with Uygur and Han ethnicities. Data showed that BMI increased with age. The centile of BMI curves, P94.46 and P99.58 for Uygur boys, P92.44 and P99.64 for Uygur girls, P85.05 and P97.26 for Han boys, P90.92 and P99.03 for Han girls, which passing through 25kg/m2 and 30kg/m2 by IOTF recommendation at age 18, were constructed. Under the basis of WGOC recommendation, the points that passing through 24kg/m2 and 28kg/m2 at age 18 was P90.54 and P98.86 for Uygur boys, P86.96 and P98.77 for Uygur girls, P78.98 and P94.72 for Han boys, Pg6.i5 and P97.56 for Han girls. The BMI cutoff points for defining overweight and obesity were suggested.2) The WGOC standard is appropriate to identifying overweight and obesity in Han ethnic children and youths in Urumqi. Regardless of the WGOC or IOTF standards, the BMI cutoff points for defining overweight and obesity in Uygur children and youths are not appropriate. The screening trial has relatively low sensitivity and may be missing part of high-risk groups. The prevalence of overweight and obesity may be underestimated. The risk of obesity is not in timely recognized. Thereby the screening effect will be weaken.3) In Uygur people, rs1052700A/T polymorphism was significantly associated with the occurrence of obesity and abdominal obesity after adjusting for covariates including age, sex, insulin, triglyceride and other factors. As compared with genotype AA, the risk with AT and TT genotypes of the occurrence of obesity were 4.485 (1.670,12.045) and 3.096 (1.161, 8.252), the risk of the occurrence of abdominal obesity (divided by waistline) were 3.709 (1.377,9.989) and 3.282 (1.226,8.784). People with AT genotypes of rs1052700 or carrying the G allele of rs6496589 have higher levels of diastolic blood pressure. No significant associations could be found between any of these polymorphisms and the studied phenotypes in Han population.4) By following-up the study subjects for a year, we observed the change of obesity state of subjects under the natural growth and development conditions. We found that the possibility of AT genotype from obesity turning to the normal body weight is 3.987 times to the possibility to maintain normal body weight compared with the AA genotype of rs1052700. Comparing the CC genotype of SNP3 with the CG+GG genotype, the possibility maintaining body weight normally is 3.03 times than the obese state of the possibility of occurrence. Under the natural self-growth condition, PLIN gene has relation to the Obesity-related measurements variable quantities, it mainly manifests that the rs6496589 impacts the absolute amount of growth and the growth rate of the body mass index, the body of CC genotype increment and velocity of increase less than CG+GG Genotype, it also shows the body mass index of the body with allele G the growth rate of large and fast, after adjusting the ethnics, ages, obesity, and other factors, rs6496589 genotype still have an impact on the body mass index of variable quantities.5) In a 7 month-period obesity intervention study, we found that simple health education group and the control group had no significant changes in various indicators. The intervention group combined with health education and physical activity, compared with simple education group and control group, the growth amount and rate of BMI decreased, the BMI-Z score which reflected growth degree of obesity in children and adolescents changes also decreased significantly, it manifested that combination of the health education and physical activity are effective in a short-term. And physical exercise can significantly reduce blood pressure and cholesterol levels among obese group but had no effect on normal weight.6) With the difference of genotypes PLIN, the different response effect of intervention of children had been observed. Among those taking part in physical exercise, comparing with CG and GG genotype, the CC genotype of rs6496589 has a lower growth amount and rate of waistline and waist height ratio, while the higher-growth measure and velocity of weight index, waistline and waist height ratio of the CC genotype of rs4578621 is higher than CG and GG genotype, even after adjustment for nations, genders and ages. It describes that subjects carrying the CC genotype of rs6496589 or the G allele of rs4578621 are more sensitive to the response of physical exercise in waistline and waist height ratio reducing.Conclusions:1) There was ethnic difference in the BMI distribution with age. We recommended using the BMI cutoff points proposed by the current study to identify overweight and obese children in Urumqi area.2) The PLIN gene in Uygur people is associated with the occurrence of obesity and abdominal obesity. Rs6496589 and rs4578621 in PLIN gene were associated with the change of obesity state under the natural growth and development conditions.3) The effect of intervention by simple health education in short-term was non-significant. The outcome of integrated interventions by health education plus physical activity are effective in a short-term, because they can effectively control the excessive growth of body mass index, and slowdown the degree of obesity in the process.4) There is a certain degree of correlation between PLIN gene polymorphisms and the effect of intervention. Therefore, in order to control and prevent obesity effectively, individualized interventions are recommended.
Keywords/Search Tags:Childhood obesity, Uygur, λmedian coefficient of variation method (LMS method), PLIN gene, Intervention
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