四川省凉山彝族和汉族人群代谢综合征患病水平及危险因素研究
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摘要
研究背景和意义
代谢综合征(Metabolic Syndrome, MS)是多种代谢成分异常聚集的病理状态,主要包括高血压、高血糖、中心性肥胖、血脂异常等。这些异常与2型糖尿病、心脑血管疾病的发生密切相关。流行病学研究证实,目前代谢综合征患病率呈现上升的趋势,尤其亚洲人群上升更为明显。由于人种的差异、诊断标准的不统一,不同国家和地区代谢综合征的患病率也不尽相同。根据美国第三次国家健康及营养调查(NHANESⅢ)显示,按ATPIII标准,美国人MS患病率为23.7%。欧洲人群患病率为15%。亚洲不同地区MS患病率也有明显差异,我国成年人MS患病率为13.7%,印度人为32%,韩国人为7.0%。
近20年来,随着中国社会经济的迅猛发展,人们的生活水平、生活方式、生活节奏、心理压力都发生了巨大变化。饮食结构变化包括高脂、高热量食物的过多摄入和体力活动的减少导致肥胖患病率和与肥胖有关的慢性病(包括高血压、2型糖尿病和心脑血管疾病)患病率呈现日益升高的趋势。1992年至2002年10年间,中国人的超重和肥胖(体重指数>24kg／m2)患病率约增加了50%。心脑血管疾病已经成为城镇和农村地区居民的主要死因。随着MS各种危险因素在个体的聚集,心脑血管疾病的死亡风险明显增加。目前,在世界范围内MS已经成为一个严重的公共卫生问题。
国内外流行病学研究已证实,MS的发生与多种环境因素和遗传因素有关,尤其是生活方式改变在MS的发生过程中起着重要作用。包括静坐为主、吸烟、饮酒、和高热量、高脂肪膳食等不健康的生活习惯。目前我国农村城镇化趋势导致生活方式的迅速变化为MS的防治带来更严峻的挑战,因此,如何在健康理念的指导下采取健康合理的生活方式是我们目前应该着重考虑的问题之一。
彝族是我国目前仍保持较原始生活方式的少数民族之一,由于环境因素、历史原因和民族文化背景不同,彝族农民的生活水平仍然远远落后于我国当前的社会经济发展水平,经济收入偏低,膳食种类单一,以洋芋、苦荞、燕麦和玉米为主,几乎很少食用肉类等高脂肪,高能量的饮食。彝族农民主要从事非机械化的手工农业劳动,体力劳动强度较大,彝族农民普遍体态偏瘦。彝族移民离开了原来农村的生活环境后,生活方式发生了很大变化,在日常生活中膳食结构多样化,高热量、高脂肪食物摄入增加,体力活动减少,肥胖程度与农民也有了明显差异。本课题组从20世纪80年代开始多次在四川凉山现场进行彝族人群高血压流行病学研究,以往的研究发现,彝族人群移居到城镇生活后,其原发性高血压患病率随移居时间增加而逐渐上升,提示彝族移民环境因素的综合改变是导致其高血压发病危险增加的重要因素。
国内迄今为止,尚无关于彝族人群MS患病率的研究报道。不同的环境因素,遗传因素如何在MS的发生过程中发挥作用尚未明确。本项研究工作拟通过探讨中国四川省凉山彝族自治州彝族农民,彝族移民和汉族居民MS的患病水平和环境因素的相互关系,即在相同遗传背景,不同生活环境下与不同遗传背景,相似生活环境下人群MS患病水平和危险因素的比较,为阐明遗传因素和环境因素对MS发生的影响提供科学依据。探讨MS的病因,为预防MS的发生,减轻家庭和社会疾病负担起着重要的作用。
目的
1)了解四川省凉山地区彝族农民、彝族移民和汉族居民MS患病水平,探讨影响MS患病率差异的环境危险因素,从而阐明遗传因素和环境因素对MS发生的影响,为建立MS人群综合防治策略提供一定的科学依据。
2)探讨胰岛素受体(INSR)基因第8外显子多态性与彝族人群和汉族人群MS的关联性。为阐明MS的遗传学病因机制提供有益的线索。
方法
本研究为横断面研究,采用分层整群抽样方法,于2007～2008年在四川省凉山彝族自治州西昌市、布拖县、昭觉县、金阳县、普格县和喜德县城镇,对20岁以上彝族农民、彝族移民和汉族居民进行流行病学调查。选取符合要求即完成身高、体重、血压测量及空腹血糖、血脂测定的受试者,共4971例确定为研究对象。其中彝族农民1535人,彝族移民1306人,汉族居民2130人。采用2004年我国中华医学会糖尿病分会MS的诊断标准。为了进一步探讨胰岛素受体基因与汉族人群、彝族人群MS的关联性,从现场调查数据库抽取所有MS的病例作为病例组,按照种族的不同分为彝族病例和汉族病例两组,根据病例数从数据库里随机选择彝族和汉族两组健康对照者,分别与病例在年龄和性别上进行频数匹配。应用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)方法对病例组和对照组胰岛素受体(INSR)基因第8外显子NsiI位点的基因型进行检测。
采用全国2000年人口普查的数据为标准进行年龄标化患率计算。应用SAS 9.1统计软件进行数据处理和统计分析,对危险因素综合分析采用多因素非条件logistic分析方法,计算OR值及其95%CI。用拟合优度卡方检验验证三种基因型的分布是否符合Hardy-Weinberg平衡,应用χ2检验分析胰岛素受体(INSR)基因第8外显子Nsil等位基因及基因型频数在病例组和对照组中分布的差异,判断该位点是否与MS关联。
结果
1.彝族农民MS标化患病率为0.9%,男、女分别为1.4%和O.5%；彝族移民MS标化患病率为11.5%,男、女分别为15.2%和7.7%；汉族MS标化患病率为7.1%,男、女分别为8.8%和5.2%。彝族移民MS患病率显著高于彝族农民和汉族居民。移民男性是本地区MS的高发人群。彝族农民男性、女性患病率差异无显著性,各年龄组MS患病率无统计学差异。汉族居民和彝族移民MS患病率均为男性高于女性,MS患病率均随年龄的增加而显著升高。
2.彝族农民超重和肥胖、高血压、糖尿病、高血糖、高甘油三酯,血脂紊乱患病率显著低于移民和汉族居民,彝族农民中无代谢组分异常者所占比例最高。彝族移民2种以上代谢组分异常率显著高于彝族农民和汉族居民。在汉族居民和彝族移民中,超重/肥胖+高血压+血脂紊乱为MS代谢异常组分最常见的聚集形式,在彝族农民中,超重/肥胖+高血糖+血脂紊乱为MS代谢异常组分最常见的聚集形式。
3.MS和环境危险因素的多元logistic回归分析显示,年龄和性别均与彝族移民和汉族居民MS有关联,而与彝族农民MS无关联。文化程度与彝族农民男性MS呈正关联,与汉族女性MS呈负关联。饮酒与彝族移民男性MS呈正关联。过量饮酒(酒精摄入量>30g／d)与汉族男性MS呈正关联。高血压、糖尿病家族史与汉族居民MS呈正关联。血浆总胆固醇水平与彝族农民男性,彝族移民男性和汉族男性MS均呈正关联。
4.汉族人群和彝族人群的基因型频数分布均符合H-W平衡定律。彝族人群中INSR基因第8外显子的基因型和等位基因频率在病例组和对照组中的频数分布均无显著性差异。汉族人群胰岛素受体(INSR)基因第8外显子NsiI的基因型和等位基因在病例组和对照组中的频数分布差异有显著性,表明汉族人群胰岛素受体(INSR)基因第8外显子NsiI多态性可能与MS关联。
结论
横断面研究结果表明,彝族移民从农村移居到城市后,MS患病率显著升高。彝族移民和汉族居民的MS患病率显著高于彝族农民,并且随年龄的增长患病率明显上升,而彝族农民MS患病率随年龄增长的趋势无显著性。MS和环境危险因素的多元logistic回归分析显示,与彝族农民MS关联的危险因素为文化程度和血浆总胆固醇水平。与彝族移民MS关联的危险因素为性别、年龄、饮酒、体力劳动强度和血浆总胆固醇水平。与汉族居民MS关联的危险因素为性别、年龄、饮酒、文化程度、高血压、糖尿病家族史和血浆总胆固醇水平。本研究通过比较相同遗传背景,不同生活环境下与不同遗传背景,相似生活环境下人群MS患病率,表明是环境因素而不是遗传因素在MS的发生过程中起着主要的决定作用,由于MS是2型糖尿病和心脑血管病的危险因素,因此从长远意义上来讲,城镇化的生活方式会明显增加心脑血管病发生的风险和疾病负担。本研究结果对于制订人群MS防治策略,从而有效地减少心脑血管疾病的危险因素、降低心脑血管病发生率和死亡率有着现实意义。
对彝族人群和汉族人群的基因多态性分析表明,在彝族人群中未发现胰岛素受体基因第8外显子NsiI多态性与MS存在关联。而在汉族人群中发现胰岛素受体基因第8外显子N2等位基因携带者可能与MS存在关联。与国内的研究结果具有一致性,提示汉族人群MS的发生可能与胰岛素受体基因有关,为进一步研究MS的遗传病因学机制提供了有益的线索。但鉴于本研究中汉族人群样本例数过少,建议今后应该增大样本量对研究结果进行进一步的验证,并且探讨基因与基因以及基因与环境交互作用所致发生MS的危险性,可能会使研究结果得到更好的论证。
Background and significance
Metabolic 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 ATPⅢdefinition 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.
Objectives
In 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.
Results
1. 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.
Conclusions
Findings 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.
代谢综合征(Metabolic Syndrome, MS)是多种代谢成分异常聚集的病理状态,主要包括高血压、高血糖、中心性肥胖、血脂异常等。这些异常与2型糖尿病、心脑血管疾病的发生密切相关。流行病学研究证实,目前代谢综合征患病率呈现上升的趋势,尤其亚洲人群上升更为明显。由于人种的差异、诊断标准的不统一,不同国家和地区代谢综合征的患病率也不尽相同。根据美国第三次国家健康及营养调查(NHANESⅢ)显示,按ATPIII标准,美国人MS患病率为23.7%。欧洲人群患病率为15%。亚洲不同地区MS患病率也有明显差异,我国成年人MS患病率为13.7%,印度人为32%,韩国人为7.0%。
近20年来,随着中国社会经济的迅猛发展,人们的生活水平、生活方式、生活节奏、心理压力都发生了巨大变化。饮食结构变化包括高脂、高热量食物的过多摄入和体力活动的减少导致肥胖患病率和与肥胖有关的慢性病(包括高血压、2型糖尿病和心脑血管疾病)患病率呈现日益升高的趋势。1992年至2002年10年间,中国人的超重和肥胖(体重指数>24kg／m2)患病率约增加了50%。心脑血管疾病已经成为城镇和农村地区居民的主要死因。随着MS各种危险因素在个体的聚集,心脑血管疾病的死亡风险明显增加。目前,在世界范围内MS已经成为一个严重的公共卫生问题。
国内外流行病学研究已证实,MS的发生与多种环境因素和遗传因素有关,尤其是生活方式改变在MS的发生过程中起着重要作用。包括静坐为主、吸烟、饮酒、和高热量、高脂肪膳食等不健康的生活习惯。目前我国农村城镇化趋势导致生活方式的迅速变化为MS的防治带来更严峻的挑战,因此,如何在健康理念的指导下采取健康合理的生活方式是我们目前应该着重考虑的问题之一。
彝族是我国目前仍保持较原始生活方式的少数民族之一,由于环境因素、历史原因和民族文化背景不同,彝族农民的生活水平仍然远远落后于我国当前的社会经济发展水平,经济收入偏低,膳食种类单一,以洋芋、苦荞、燕麦和玉米为主,几乎很少食用肉类等高脂肪,高能量的饮食。彝族农民主要从事非机械化的手工农业劳动,体力劳动强度较大,彝族农民普遍体态偏瘦。彝族移民离开了原来农村的生活环境后,生活方式发生了很大变化,在日常生活中膳食结构多样化,高热量、高脂肪食物摄入增加,体力活动减少,肥胖程度与农民也有了明显差异。本课题组从20世纪80年代开始多次在四川凉山现场进行彝族人群高血压流行病学研究,以往的研究发现,彝族人群移居到城镇生活后,其原发性高血压患病率随移居时间增加而逐渐上升,提示彝族移民环境因素的综合改变是导致其高血压发病危险增加的重要因素。
国内迄今为止,尚无关于彝族人群MS患病率的研究报道。不同的环境因素,遗传因素如何在MS的发生过程中发挥作用尚未明确。本项研究工作拟通过探讨中国四川省凉山彝族自治州彝族农民,彝族移民和汉族居民MS的患病水平和环境因素的相互关系,即在相同遗传背景,不同生活环境下与不同遗传背景,相似生活环境下人群MS患病水平和危险因素的比较,为阐明遗传因素和环境因素对MS发生的影响提供科学依据。探讨MS的病因,为预防MS的发生,减轻家庭和社会疾病负担起着重要的作用。
目的
1)了解四川省凉山地区彝族农民、彝族移民和汉族居民MS患病水平,探讨影响MS患病率差异的环境危险因素,从而阐明遗传因素和环境因素对MS发生的影响,为建立MS人群综合防治策略提供一定的科学依据。
2)探讨胰岛素受体(INSR)基因第8外显子多态性与彝族人群和汉族人群MS的关联性。为阐明MS的遗传学病因机制提供有益的线索。
方法
本研究为横断面研究,采用分层整群抽样方法,于2007～2008年在四川省凉山彝族自治州西昌市、布拖县、昭觉县、金阳县、普格县和喜德县城镇,对20岁以上彝族农民、彝族移民和汉族居民进行流行病学调查。选取符合要求即完成身高、体重、血压测量及空腹血糖、血脂测定的受试者,共4971例确定为研究对象。其中彝族农民1535人,彝族移民1306人,汉族居民2130人。采用2004年我国中华医学会糖尿病分会MS的诊断标准。为了进一步探讨胰岛素受体基因与汉族人群、彝族人群MS的关联性,从现场调查数据库抽取所有MS的病例作为病例组,按照种族的不同分为彝族病例和汉族病例两组,根据病例数从数据库里随机选择彝族和汉族两组健康对照者,分别与病例在年龄和性别上进行频数匹配。应用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)方法对病例组和对照组胰岛素受体(INSR)基因第8外显子NsiI位点的基因型进行检测。
采用全国2000年人口普查的数据为标准进行年龄标化患率计算。应用SAS 9.1统计软件进行数据处理和统计分析,对危险因素综合分析采用多因素非条件logistic分析方法,计算OR值及其95%CI。用拟合优度卡方检验验证三种基因型的分布是否符合Hardy-Weinberg平衡,应用χ2检验分析胰岛素受体(INSR)基因第8外显子Nsil等位基因及基因型频数在病例组和对照组中分布的差异,判断该位点是否与MS关联。
结果
1.彝族农民MS标化患病率为0.9%,男、女分别为1.4%和O.5%；彝族移民MS标化患病率为11.5%,男、女分别为15.2%和7.7%；汉族MS标化患病率为7.1%,男、女分别为8.8%和5.2%。彝族移民MS患病率显著高于彝族农民和汉族居民。移民男性是本地区MS的高发人群。彝族农民男性、女性患病率差异无显著性,各年龄组MS患病率无统计学差异。汉族居民和彝族移民MS患病率均为男性高于女性,MS患病率均随年龄的增加而显著升高。
2.彝族农民超重和肥胖、高血压、糖尿病、高血糖、高甘油三酯,血脂紊乱患病率显著低于移民和汉族居民,彝族农民中无代谢组分异常者所占比例最高。彝族移民2种以上代谢组分异常率显著高于彝族农民和汉族居民。在汉族居民和彝族移民中,超重/肥胖+高血压+血脂紊乱为MS代谢异常组分最常见的聚集形式,在彝族农民中,超重/肥胖+高血糖+血脂紊乱为MS代谢异常组分最常见的聚集形式。
3.MS和环境危险因素的多元logistic回归分析显示,年龄和性别均与彝族移民和汉族居民MS有关联,而与彝族农民MS无关联。文化程度与彝族农民男性MS呈正关联,与汉族女性MS呈负关联。饮酒与彝族移民男性MS呈正关联。过量饮酒(酒精摄入量>30g／d)与汉族男性MS呈正关联。高血压、糖尿病家族史与汉族居民MS呈正关联。血浆总胆固醇水平与彝族农民男性,彝族移民男性和汉族男性MS均呈正关联。
4.汉族人群和彝族人群的基因型频数分布均符合H-W平衡定律。彝族人群中INSR基因第8外显子的基因型和等位基因频率在病例组和对照组中的频数分布均无显著性差异。汉族人群胰岛素受体(INSR)基因第8外显子NsiI的基因型和等位基因在病例组和对照组中的频数分布差异有显著性,表明汉族人群胰岛素受体(INSR)基因第8外显子NsiI多态性可能与MS关联。
结论
横断面研究结果表明,彝族移民从农村移居到城市后,MS患病率显著升高。彝族移民和汉族居民的MS患病率显著高于彝族农民,并且随年龄的增长患病率明显上升,而彝族农民MS患病率随年龄增长的趋势无显著性。MS和环境危险因素的多元logistic回归分析显示,与彝族农民MS关联的危险因素为文化程度和血浆总胆固醇水平。与彝族移民MS关联的危险因素为性别、年龄、饮酒、体力劳动强度和血浆总胆固醇水平。与汉族居民MS关联的危险因素为性别、年龄、饮酒、文化程度、高血压、糖尿病家族史和血浆总胆固醇水平。本研究通过比较相同遗传背景,不同生活环境下与不同遗传背景,相似生活环境下人群MS患病率,表明是环境因素而不是遗传因素在MS的发生过程中起着主要的决定作用,由于MS是2型糖尿病和心脑血管病的危险因素,因此从长远意义上来讲,城镇化的生活方式会明显增加心脑血管病发生的风险和疾病负担。本研究结果对于制订人群MS防治策略,从而有效地减少心脑血管疾病的危险因素、降低心脑血管病发生率和死亡率有着现实意义。
对彝族人群和汉族人群的基因多态性分析表明,在彝族人群中未发现胰岛素受体基因第8外显子NsiI多态性与MS存在关联。而在汉族人群中发现胰岛素受体基因第8外显子N2等位基因携带者可能与MS存在关联。与国内的研究结果具有一致性,提示汉族人群MS的发生可能与胰岛素受体基因有关,为进一步研究MS的遗传病因学机制提供了有益的线索。但鉴于本研究中汉族人群样本例数过少,建议今后应该增大样本量对研究结果进行进一步的验证,并且探讨基因与基因以及基因与环境交互作用所致发生MS的危险性,可能会使研究结果得到更好的论证。
Background and significance
Metabolic 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 ATPⅢdefinition 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.
Objectives
In 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.
Results
1. 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.
Conclusions
Findings 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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