| Background and significanceMetabolic syndrome (MS) is characterized by a clustering of risk factors that predispose individuals to cardiovascular disease (CVD) and type 2 Diabetes. These factors include abdominal obesity, high triglycerides, low HDL cholesterol levels, high blood pressure and high fasting plasma glucose. Epidemiological studies have showed that the prevalence of MS is on the rise and ethnic predisposition is suggested among Asian populations. Using the NCEP ATPâ…¢definition for MS, the prevalence of MS is 23% in American and 15% in European populations. As for Asians, the prevalence varies from 7% in Korea to 13.7% in China and 32% in India, which might partially be due to the use of different definitions for MS and the ethnicity of the population.Over the past two decades, China has experienced rapid socioeconomic growth, resulting in lifestyle changes with higher fat intake and lighter physical activities which have promoted the development of MS and other chronic diseases in the population. From 1992 to 2002, the prevalence of overweight and obesity and obesity-related chronic diseases have increased considerably (50%) in China. CVD is therefore becoming more prevalent and a leading cause of death in urban and rural areas. The aggregate risk factors of MS are associated with marked increase in mortality risk of cardiovascular disease, making MS an important public health problem in China.Most domestic and foreign epidemiological studies have shown that the MS is affected by kinds of environment and genetic factors. Dramatic changes in lifestyle appear to play a primary role in the presence of MS. Some lifestyle behaviors, including sedentary activities, smoking, alcohol intake and unhealthy dietary habits are associated with MS in adults. The urbanized trend in China has contributed to lifestyle changes, which brings more serious situation for MS prevention and treatment. Currently, the most challenging problem is related to promoting healthy lifestyle under reasonable guidance.Yi people belong to one of the ethnic minorities who have preserved primitive lifestyle in China. At present, the standard of living among the Yi farmers are still more lagging behind the current economic and social developments due to environmental conditions, cultural background and other factors. Limited family income reflect that they have few opportunities for eating high-fat and high-energy foods such as meats and processed foods. Their principal components of diet are potatoes, corns, buckwheat, oats and rice. Agriculture is the main source of income for Yi people in the area and they farm and grow most of their own food stuff with primitive tools, with extremely heavy agricultural labor, ended up with very lean figure for most of the population. When migrants leave their land to live and work in urban areas, they have more opportunities for consuming abundant foods and sedentary activities and experience a transition from traditional to more typical urbanized lifestyle with higher fat intake and lighter physical activities. The prevalence of hypertension in Yi farmers and Yi migrants were surveyed in liangshan prefecture, Sichuan province in the 1980's with results showing that the prevalence of hypertension was significant higher with increasing migration time in Yi migrants, and that the change in prevalence of hypertension was most likely to be related to the comprehensive alteration of environmental factors.Few literature has been published regarding the prevalence of MS in Yi people in China, The effects of different environmental and genetic factors on MS are still remain unclear. The goal of this study is to determine the prevalence of MS and associated factors among Yi farmers, Yi migrants and Han residents, and to indicate whether environmental factors or genetic factors have predominantly contributed to the progression of MS by comparing populations with similar genetic background but different environmental circumstances, and populations with same environmental circumstances but different genetic background. Hopefully, these findings can make contributions to elucidate the mechanism of MS, developing primary prevention and control strategies, thus to reduce the increased societal burden of CVD in China.ObjectivesIn this dissertation, our aims are:1. To determine the prevalence of MS and associated environmental factors among Yi farmers, Yi migrants and Han population, and to analyze environmental and genetic effects on the MS.2. To provide evidence that whether environmental factors or genetic factors might have predominantly contributed to the progression of MS. Through this study, strategies on the experience of prevention on MS will also be tackled upon.3. To explore the relationship between the polymorphism of insulin receptor gene exon 8 and MS in the Yi and the Han people. Methods:A cross-sectional survey was conducted among Yi farmers, Yi migrants and Han residents living in Xichang city and Butuo, Zhaojue, Jinyang, Puge, Xide counties, in Sichuan province. Using stratified multistage cluster sampling method, a sample of 1,535 Yi farmers,1,306 Yi migrants and 2,130 Han residents aged over 20 years were selected from 2007 to 2008. Questionnaire survey, anthropometric measurement and blood test were carried out. The MS was defined by the definition proposed by the Chinese Society for Diabetes Mellitus (CDS) in 2004.Based on the cross-sectional survey, two case-control studies were designed according to different nationalities. This study selected MS cases as case group and unrelated healthy control individuals as control group with frequency matching of sex and age. Polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) were adopted to examine the individual genotype.All data analyses were performed using SAS 9.1 with P< 0.05 considered to be statistically significant.'2000 national census data' was used to represent the data for reference population. Multiple logistic regression analysis was performed to estimate the risk of MS associated environmental factors. The odds ratios (OR) were presented together with their 95% CI. Goodness of fit x2 test was used to detect whether the genotypic distribution was in Hardy-Weinberg equilibrium. The differences of allele and genotype distribution between the MS case and control group were detected by x2 test.Results1. The age-standardized prevalence of MS was 0.9% in Yi farmers (male:1.4%, female: 0.5%), and 11.5% in Yi migrants (male:15.2%, female:7.7%), and 7.1% in Han residents (male:8.8%, female:5.2%). The age-standardized prevalence was higher in Yi migrants than in Yi farmers and Han residents. Prevalence of MS in Male Yi migrants was the highest in local district.2. The prevalence of MS was remarkably more prevalent in men compared to women among Yi migrants and Han people, but no significant sex difference in Yi farmers was found. The prevalence of MS increased significantly with increasing age in both sexes in Yi migrants and Han people, whereas Yi farmers having low prevalence rates of MS with no adult age-related rise.3. Compared with Yi migrants and Han residents, the prevalence rates of overweight and obesity, high fasting glucose, diabetes, hypertension and dyslipidemia were all significantly low in Yi farmers. When comparing to other populations, the proportion without metabolize abnormity in Yi farmers was the highest (53.9%) among all the three groups. The proportion with 2 or more metabolize abnormity in Yi migrants was higher than that in Han residents and Yi farmers. The most concentrating modes in every abnormal metabolic component were overweight/obesity+hypertension+dyslipidemia in both Yi migrants and Han population whereas overweight/obesity+high fasting glucose +dyslipidemia in Yi farmers.4. Result from the multiple logistic regression showed that sex and age were significantly associated with MS in both Yi migrants and Han residents but there was no association with MS in Yi farmer. For male Yi farmer, high education level and high cholesterol level were contributing risk factors for MS. but in male Yi migrant, alcohol intake and high cholesterol level were contributing risk factors for MS. For male Han residents, family histories of having hypertension or diabetes, excessive alcohol intake (alcohol>30g/d) and high cholesterol level were contributing risk factors for MS. For female Han residents, family histories of having hypertension or diabetes were contributing risk factors for MS, but high education level was protective to MS.5. The goodness-of-fit test showed that the genotype frequency distributions of insulin receptor gene exon 8 were not deviated from the Hardy-Weinberg equilibrium. No association between the genotype and alleles of INSR gene exon 8 and MS was found in the Yi people. There was significant difference for the frequencies of alleles of INSR gene exon 8 in the Han people. These findings indicating that a significant association between INSR gene exon 8 and MS was existed in the Han population and this result seemed helpful in better understanding the genetic basis of the MS.ConclusionsFindings from this cross-sectional study indicated that with the change of environmental condition, the prevalence of the MS might become higher when Yi farmer migrated to live in the county or township. Yi farmers used to have low prevalence rates of MS with no adult age-related rise, the prevalence of MS and the trend of prevalence with increasing age in Yi migrantes with Han residents much higher than the Yi farmers. Data from the multivariate analysis showed that:education level and cholesterol level were associated with MS in Yi farmers. But for Yi migrant, sex, age, physical activity, alcohol intake and cholesterol level were associated with the MS. For Han residents, sex, age, education level, family histories of having hypertension or diabetes, excessive alcohol intake (alcohol>30g/d) and high cholesterol level were associated with the MS. In this study, our results demonstrated that environmental factors, rather than genetic factors, might have predominantly contributed to the progression of MS by comparing populations with similar genetic background but different environmental circumstances, and populations with same environmental circumstances but different genetic background. Since MS is a major risk factor for type 2 Diabetes and CVD, changes of lifestyle may also be responsible for the increase of risk on CVD in the long run. Hopefully the results from our study may somehow contribute to the development of a MS prevention strategy that will lead to the reduction of related risks associated to CVD. No association between the genotype and alleles of INSR gene exon 8 and MS was found in the Yi population. Significant difference was found in the frequencies of alleles of INSR gene exon 8 among the Han people which indicating the existence of an association between INSR gene exon 8 and MS. This finding seemed to be helpful for a better understanding on the genetic basis of MS. However, given the small number of sample cases in Han population, future research is needed for further verification. Also, it is important to further explore the potential gene-gene or gene-environment interaction that will contribute to the notification of potential risks on MS.
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