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杭州市区人群主观乳糖不耐受流行病学调查及乳糖酶基因多态性研究

发布时间:2018-08-27 16:21
【摘要】: 1杭州市区人群主观乳糖不耐受流行病学调查 1.1杭州市区人群乳糖不耐受发生率调查及相关因素分析 背景:由于乳糖酶的缺乏,很多人群摄入含一定量乳糖的牛奶后出现腹部不适症状,主观认为是乳糖不耐受患者,因此避免食用乳制品,这可能会给他们带来长期的健康危害。而目前却缺乏有关人群主观乳糖不耐受的报道以及由此引起的牛奶及奶制品摄入的变化。 目的:了解杭州市区人群中主观乳糖不耐受的发生率,并对其相关因素进行探讨。 方法:按照分层整群随机抽样调查原则,在杭州市抽取3个区,然后在每个区中各抽取一个社区作为调查点,对社区居民进行抽样调查。采用问卷调查的方式,以面对面询问的方式回答问卷。问卷内容包括个人饮用牛奶及奶制品情况(包括种类及量),饮用牛奶及奶制品后是否出现腹部不适症状(包括腹胀、胃肠胀气、腹鸣、腹痛、腹泻、恶心、呕吐等),以及生活事件量表、医院焦虑抑郁量表和肠道症状量表。采用SPSS 13.0统计软件来进行数据的统计分析,Mann-Whitney U test方法用于非正态分布的两组之间的比较,Logistic回归分析用于评价乳糖摄入在性别、年龄段之间有无差异以及主观乳糖不耐受者与乳糖耐受者之间的多因素分析。 结果:本研究共调查了800人,有68人因调查问卷资料填写不完整而剔除出本研究,最后纳入分析的有效调查问卷有732份,男性261例,女性471例,年龄17-75岁,平均46.12±14.77岁。主观乳糖不耐受者135例,男性40例,女性95例,平均年龄45.59±14.60岁,其中轻度腹部不适111例,中度不适16例,重度不适8例。人群中以牛奶消费为主,其次是酸奶及调味奶,而奶粉及炼乳或浓缩乳消费者很少,大多数消费酸奶量多的人群却对牛奶的消费量相对少。人群乳制品消费种类不同的原因中,无饮用乳制品习惯的有413例(56.4%,413/732),有166例认为不喜欢某种(些)乳制品的口味(22.7%),有135例认为自己饮用乳制品后出现腹部症状(18.4%),只有18例(2.5%)认为经济上难以承受对于乳制品的每日消费。乳制品中乳糖的摄入量,女性高于男性,差异有统计学意义,且随着年龄的增长,乳糖摄入量逐渐减少,30岁以下人群和60岁以上人群间乳糖摄入存在显著性差异。主观乳糖不耐受者乳制品及乳糖的摄入量较无症状的人群明显减少,差异有统计学意义。主观乳糖不耐受者与耐受者在性别、年龄、家庭人均月收入、职业及受教育程度等方面无显著性差异。在焦虑评分、抑郁评分、生活应激评分及肠道症状评分方面,主观乳糖不耐受者均高于耐受者,但仅焦虑评分的差异有统计学意义。 结论:杭州市区人群随着年龄的增长,乳制品及乳糖摄入量逐渐减少。人群中主观乳糖不耐受的比率较高,且主观乳糖不耐受者乳制品及乳糖的摄入量较无症状人群明显减少。焦虑状态水平在主观乳糖不耐受者中高于乳糖耐受者。 1.2主观乳糖不耐受和实际乳糖不耐受的相关性的研究 背景:关于乳糖不耐受的研究很多,然而对于乳糖不耐受的误解仍然比较普遍。主观乳糖不耐受人群中部分实际上能正常消化乳糖,因此对主观乳糖不耐受人群的判定很重要。 目的:探讨主观乳糖不耐受与实际乳糖不耐受的情况,评价主观乳糖不耐受与实际乳糖不耐受的相关性。 方法:研究对象为在杭州居住的人群,根据纳入和排除标准最终确定入选的研究对象。对研究对象采用问卷调查的方式,以面对面询问的方式回答问卷。问卷内容包括个人饮用牛奶及奶制品情况(包括种类及量),饮用牛奶及奶制品后是否出现腹部不适症状(包括腹胀、排气增多、腹鸣、腹痛、腹泻、恶心、呕吐等),以及最近三个月内腹痛及大便情况,和生活事件量表、医院焦虑抑郁量表和肠道症状量表。个体饮用牛奶及奶制品后出现腹部不适症状或因上述腹部症状而拒绝饮用者,判定为主观乳糖不耐受。所有研究对象均行乳糖氢呼气试验检查。若氢气浓度升高超过基础值20ppm以上水平并伴有消化道症状或出现消化道症状而不论氢气浓度变化是否超过基础值20ppm,判定为乳糖不耐受;氢气浓度升高超过基础值20ppm以上水平但不伴有消化道症状为乳糖消化不良;氢气浓度变化不超过基础值20ppm水平,且不伴有消化道症状为乳糖正常消化。记录氢呼气试验检查中和检查后12小时内的腹部症状评分,症状评分为摄入乳糖后12h内各症状评分系数与其严重程度乘积之和。采用SPSS 13.0统计软件来进行统计分析。卡方检验用于主观乳糖不耐受与氢呼气试验检测的实际乳糖不耐受之间的比较,Logistic回归分析用于评价主观乳糖不耐受者中三种乳糖消化吸收类型之间的多因素分析。单因素方差分析用于评价乳糖摄入在性别之间有无差异,Mann-Whitney U test方法用于非正态分布的两组之间的比较。 结果:共有209人纳入本研究,且都经历了20g乳糖氢呼气试验检查。209例中,乳糖不耐受者139例(66.5%),男性74例,女性65例;乳糖消化不良37例(17.7%),男性17例,女性20例;乳糖正常消化者33例(15.8%),男性14例,女性19例。三种类型在男女性别方面无统计学差异。本研究中主观乳糖不耐受54例,占本研究对象的25.8%(54/209),其中经乳糖氢呼气试验诊断为乳糖不耐受42例(77.8%,42/54),乳糖消化不良5例(9.2%),乳糖正常消化7例(13.0%)。问卷调查的主观乳糖不耐受对于实际乳糖不耐受判定的敏感度为30.2%(42/139),特异度为82.9%(58/70),阳性预测值为77.8%(42/54),阴性预测值为37.4%(58/155)。54例主观乳糖不耐受者采用ROMEⅢ标准来诊断,有35例为肠易激综合征,其中实际乳糖不耐受29例,乳糖消化不良3例,乳糖正常消化3例。主观乳糖不耐受中的实际乳糖不耐受、乳糖消化不良及乳糖正常吸收与肠易激综合征之间无统计学差异(p=0.394)。主观乳糖不耐受者中三种乳糖消化吸收的类型之间在性别、年龄、家庭人均月收入、职业及受教育程度、焦虑评分、抑郁评分、生活应激评分及肠道症状评分等方面均无统计学差异。 结论:主观乳糖不耐受不能准确地反应中国人群中实际乳糖不耐受情况。主观乳糖不耐受的灵敏度低且特异度不够高,不能很好地判定实际乳糖不耐受,但其有一定的阳性预测值,有助于提高实际乳糖不耐受的检出率。对于主观乳糖不耐受者,应行乳糖氢呼气试验以明确其具体类型并排除被误认为是主观乳糖不耐受的人群。另外,乳糖氢呼气试验能发现一些潜在的乳糖不耐受者。 2乳糖不耐受与乳糖消化不良间差异的机制研究 背景:在乳糖酶缺乏者中,一些人群表现为乳糖消化不良,而另一些人群则表现为乳糖不耐受,且不耐受症状各异,对于乳糖不耐受与乳糖消化不良间差异的机制目前尚未十分明确。 目的:探讨乳糖不耐受与乳糖消化不良在胃肠道动力及肠道菌群间的差异,以及它们之间的相互影响。 方法:对无器质性疾病的成年人,行乳糖氢呼气试验检查及记录腹部症状(腹鸣、腹胀、腹痛及腹泻等),确定其是否为乳糖不耐受、乳糖消化不良或乳糖正常消化。评估乳糖不耐受者的腹部症状评分,并通过氢呼气试验评价口盲肠转运时间。运用荧光原位杂交技术,选择5种特异性的探针检测乳糖不耐受、乳糖消化不良及乳糖正常消化者的肠道菌群情况。 结果:163例研究对象中,男性80例,女性83例,其中乳糖不耐受有117例(男性62例,女性55例),乳糖消化不良24例(男性9例,女性15例),乳糖正常消化22例(男性9例,女性13例)。乳糖不耐受与乳糖消化不良在年龄及性别之间无统计学差异。乳糖不耐受的口盲肠转运时间为54.23±30.12分钟,而乳糖消化不良的口盲肠转运时间为77.50±31.49分钟,两者间差异有统计学意义,且口盲肠转运时间的OR值为0.977,有统计学意义(p=0.003)。运用荧光原位杂交技术,发现肠道总细菌量及4种特异性探针所对应的肠道细菌量在乳糖不耐受、乳糖消化不良及乳糖正常消化三者间存在差异。与Bac303探针杂交的拟杆菌属和普霍沃勒菌属及与Erec482探针杂交的直肠真杆菌-球形梭菌属,在乳糖不耐受者中明显高于乳糖消化不良和乳糖正常消化者;而与Bif164杂交的双歧杆菌属及与Lab722杂交的乳杆菌属,在乳糖不耐受者中明显低于乳糖消化不良和乳糖正常消化者,p值均0.05,差异有统计学意义。 结论:口盲肠转运时间和肠道菌群组成变化与乳糖不耐受密切相关。乳糖不耐受者的口盲肠转运时间较乳糖消化不良者明显缩短。乳糖不耐受、乳糖消化不良及乳糖正常消化三者间的肠道菌群组成存在显著差异。乳糖不耐受者的肠道拟杆菌属和普霍沃勒菌属及直肠真杆菌-球形梭菌属明显高于乳糖消化不良和乳糖正常消化者,而双歧杆菌属及乳杆菌属明显低于乳糖消化不良和乳糖正常消化者。 3杭州市区人群乳糖酶基因多态性与乳糖酶持续的相关性的研究 背景:乳糖酶持续的频率在不同人群中存在很大的差异,乳糖酶基因的T-13910位点在欧洲人群中与乳糖酶持续密切相关,然而其在非洲人群和中国北部人群并无明显的相关性。 目的:探讨杭州市区人群中乳糖酶基因T-13910等位基因位点情况,以及邻近基因的单核苷酸多态性与乳糖酶持续的相关性。 方法:对无器质性疾病的杭州市区成年人,行乳糖氢呼气试验检查,确定其是否为乳糖酶持续或乳糖酶不持续,并抽取外周血行全血DNA提取,进行PCR扩增及测序,将DNA测序结果进行比对分析以明确T-13910等位基因位点情况,并发现有无新的基因多态性位点。然后将乳糖酶基因型与乳糖酶表现型进行比较及相关性分析。 结果:有163例纳入研究,其中男性80例,女性83例,年龄21-70岁,平均年龄42.20±11.45岁。经乳糖氢呼气试验确定为乳糖酶持续型22例(13.5%,22/163),男性9例,女性13例;另141例为乳糖酶不持续型(86.5%,141/163),男性71例,女性70例。在141例乳糖酶不持续型中,乳糖不耐受117例(83.0%),乳糖消化不良24例(17.0%)。乳糖酶持续与乳糖酶不持续在男女性别方面无统计学差异。在所有被研究人群中均未检测到T-13910基因多态性位点,均为纯合子C/C-13910。也发现人群中存在多个不同于C/T-13910的新的单核苷酸多态性位点,它们分别为C/T-13908、A/C-13926、G/A-14010、T/G-13951、C/T-13952,其中A/C-13926出现在3例不同的DNA序列中,在2例不同的DNA序列中发现C/T-13908多态性位点,G/A-14010单核苷酸多态性位点存在于1例中,而T/G-13951及C/T-13952多态性位点存在于同一例DNA序列中。T-13908等位基因均存在于乳糖酶持续中;C-13926等位基因均存在于乳糖酶不持续中,且T-13908等位基因与乳糖酶持续相关,有统计学意义(p=0.017)。而C-13926等位基因与乳糖酶不持续的相关性无统计学意义。另外,A-14010、G-13951、T-13952等位基因多态性位点与乳糖酶表现型的相关性亦无统计学意义。 结论:首次发现乳糖酶基因在杭州市区人群中有多个新的单核苷酸多态性位点,包括T-13908、C-13926、A-14010、G-13951、T-13952等位基因。T-13908等位基因可能与杭州市区人群的乳糖酶持续相关。乳糖酶持续在杭州市区人群比较少见,乳糖酶基因上游的T-13910等位基因位点的频率很低。T-13910等位基因位点检测法在杭州市区人群中不能预测乳糖酶持续。
[Abstract]:Epidemiological survey of Subjective Lactose Intolerance in 1 urban population of Hangzhou
Prevalence of lactose intolerance and related factors in 1.1 urban population of Hangzhou
BACKGROUND: Due to the lack of lactase, many people suffer from abdominal discomfort after intake of milk containing a certain amount of lactose. They are subjectively considered to be patients with lactose intolerance. Therefore, avoidance of dairy products may cause long-term health hazards to them. However, there are no reports on Subjective Lactose Intolerance in the population and its causes. Changes in intake of milk and dairy products.
Objective: To investigate the incidence of Subjective Lactose Intolerance in Hangzhou urban population and to explore the related factors.
Methods: According to the principle of stratified cluster random sampling survey, three districts were selected in Hangzhou, and then one community in each district was selected as the survey point to conduct a sampling survey of community residents. Types and doses, abdominal discomfort symptoms (including abdominal distention, gastrointestinal distention, ringing, abdominal pain, diarrhea, nausea, vomiting, etc.) and life events scale, Hospital Anxiety and depression scale and intestinal symptom scale. SPSS 13.0 statistical software was used for statistical analysis of the data. Mann-Whitney U test method was used for statistical analysis. Logistic regression analysis was used to assess the differences in lactose intake between the two groups with non-normal distribution, gender, age, and multivariate analysis of Subjective Lactose Intolerance and lactose tolerance.
Results: A total of 800 subjects were investigated, 68 of them were excluded from the study because of incomplete questionnaire data. At last, 732 valid questionnaires were included in the analysis, including 261 males and 471 females, aged 17-75, with an average age of 46.12 + 14.77 years. There were 111 cases of moderate and mild abdominal discomfort, 16 cases of moderate discomfort and 8 cases of severe discomfort. Milk consumption was the main factor, followed by yoghurt and seasoned milk, while milk powder and condensed milk or concentrated milk consumers were few. Most of the people who consumed more yoghurt consumed less milk. There were 413 (56.4%, 413/732) dairy habits, 166 (22.7%) who thought they did not like the taste of certain (some) dairy products, 135 (18.4%) who thought they had abdominal symptoms after drinking dairy products, and only 18 (2.5%) who thought they could not afford the daily consumption of dairy products financially. The intake of dairy products and lactose in subjects with subjective lactose intolerance was significantly lower than that in asymptomatic subjects, and the difference was statistically significant. There was no significant difference in anxiety score, depression score, life stress score and intestinal symptoms score, but the difference was statistically significant.
Conclusion: The intake of dairy products and lactose decreases with age in Hangzhou urban population. The rate of Subjective Lactose intolerance is higher, and the intake of dairy products and lactose in Subjective Lactose Intolerance group is significantly lower than that in asymptomatic group. The level of anxiety in Subjective Lactose Intolerance group is higher than that in lactose intolerance group.
1.2 study on the correlation between Subjective Lactose Intolerance and actual lactose intolerance
BACKGROUND: There are many studies on lactose intolerance, but misunderstandings about lactose intolerance are still widespread. Some of the subjects with subjective lactose intolerance can actually digest lactose normally, so it is important to judge the subjects with Subjective Lactose intolerance.
Objective: To investigate the relationship between Subjective Lactose Intolerance and actual lactose intolerance.
Methods: The subjects were selected according to the inclusion and exclusion criteria of the people living in Hangzhou. The subjects were interviewed face-to-face to answer the questionnaires. The questionnaires included personal drinking of milk and dairy products (including types and quantities), and whether or not they drank milk and dairy products after drinking. Symptoms of abdominal discomfort (including abdominal distention, increased exhaust, abdominal tinnitus, abdominal pain, diarrhea, nausea, vomiting, etc.) and abdominal pain and feces in the last three months, life events scale, Hospital Anxiety and depression scale and intestinal symptom scale. Individuals who drink milk and dairy products develop abdominal discomfort or refuse to drink because of the above abdominal symptoms Lactose intolerance was defined as subjective lactose intolerance. All subjects underwent lactose-hydrogen breath test. If hydrogen concentration increased above the baseline level of 20 ppm and accompanied by gastrointestinal symptoms or gastrointestinal symptoms, whether or not the change in hydrogen concentration exceeded the baseline value of 20 ppm, it was defined as lactose intolerance; if hydrogen concentration increased beyond the baseline level of 20 ppm, lactose intole Lactose dyspepsia was found at baseline level of 20 ppm or above but without digestive tract symptoms; hydrogen concentration did not exceed baseline level of 20 ppm, and normal digestion of lactose was not found in patients with digestive tract symptoms. SPSS 13.0 statistical software was used for statistical analysis. Chi-square test was used for comparing Subjective Lactose intolerance with actual lactose intolerance detected by hydrogen breath test. Logistic regression analysis was used to evaluate the multivariate analysis of three types of lactose digestion and absorption in Subjective Lactose intolerance. Univariate analysis of variance was used to assess gender differences in lactose intake, and Mann-Whitney U test was used to compare two groups with non-normal distribution.
Results: A total of 209 subjects were enrolled in the study and all underwent 20g lactose hydrogen breath test. Among 209 subjects, 139 (66.5%) were lactose intolerant, 74 males and 65 females, 37 (17.7%) were lactose dyspepsia, 17 males and 20 females, 33 (15.8%) were lactose normal digestion, 14 males and 19 females. There were 54 cases of Subjective Lactose intolerance, accounting for 25.8% (54/209). 42 cases (77.8%, 42/54), 5 cases (9.2%) of lactose dyspepsia and 7 cases (13.0%) of lactose intolerance were diagnosed by lactose hydrogen breath test. The ROME III criteria were used to diagnose 54 cases of Subjective Lactose intolerance, 35 cases of irritable bowel syndrome, including 29 cases of actual lactose intolerance, 3 cases of lactose dyspepsia and 3 cases of normal lactose digestion. There was no significant difference between actual lactose intolerance, lactose dyspepsia, normal lactose uptake and irritable bowel syndrome (p = 0.394). There were three types of lactose digestion and absorption among subjects with Subjective Lactose intolerance, including sex, age, family monthly income, occupation and education, anxiety score, depression score, life stress score and intestine. There was no significant difference in symptom scores.
CONCLUSION: Subjective lactose intolerance can not accurately reflect the actual lactose intolerance in Chinese population. Subjective lactose intolerance has low sensitivity and specificity. It can not be used to judge actual lactose intolerance well, but it has a certain positive predictive value, which is helpful to improve the detection rate of actual lactose intolerance. Lactose hydrogen breath test should be performed to identify the specific type and exclude those mistaken for Subjective Lactose intolerance. In addition, Lactose hydrogen breath test can identify some potential lactose intolerants.
2 the mechanism of lactose intolerance and lactose dyspepsia
BACKGROUND: In lactase deficiency patients, some people show lactose intolerance, while others show lactose intolerance with different symptoms. The mechanism of the difference between lactose intolerance and lactose dyspepsia is still unclear.
Objective: To investigate the differences between lactose intolerance and lactose dyspepsia in gastrointestinal motility and intestinal flora, and their interaction.
Methods: Lactose-hydrogen breath test was used to examine and record the abdominal symptoms (ringing, distention, abdominal pain, diarrhea, etc.) in adults without organic diseases to determine whether they were lactose intolerance, lactose dyspepsia or normal lactose digestion. Five specific probes were selected to detect intestinal flora in lactose intolerance, lactose dyspepsia and normal lactose digestion by fluorescence in situ hybridization.
Results: Of the 163 subjects, 80 were males and 83 were females, 117 were lactose intolerance (62 males and 55 females), 24 were lactose dyspepsia (9 males and 15 females), and 22 were lactose normal digestion (9 males and 13 females). There was no significant difference in age and sex between lactose intolerance and lactose dyspepsia. The oral-cecum transit time was 54.23 (+ 30.12) minutes, while the oral-cecum transit time of lactose dyspepsia was 77.50 (+ 31.49) minutes. The OR value of the oral-cecum transit time was 0.977, which was statistically significant (p = 0.003). The total bacterial count in the intestine and the four specific probes were detected by fluorescence in situ hybridization (FISH). Bacterioids hybridized with Bac303 probe, Prohovolera and Clostridium sphaeroides hybridized with Erec482 probe were significantly higher in lactose intolerance than in lactose intolerance and lactose normal digestion. However, Bifidobacterium hybridized with Bif164 and Lactobacillus hybridized with Lab722 were significantly lower in lactose intolerant patients than those with lactose dyspepsia and normal lactose digestion, P values were 0.05, the difference was statistically significant.
CONCLUSION: The oral-cecum transit time and intestinal microflora composition are closely related to lactose intolerance. The oral-cecum transit time of lactose intolerant patients is significantly shorter than that of lactose intolerant patients. There are significant differences in intestinal microflora composition among lactose intolerance, lactose dyspepsia and normal lactose digestion. Bacillus, Prokhovella and Clostridium sphaeroides were significantly higher than those of lactose dyspepsia and lactose normal digestion, while Bifidobacterium and Lactobacillus were significantly lower than those of lactose dyspepsia and lactose normal digestion.
Correlation between lactase gene polymorphism and lactase persistence in 3 urban population of Hangzhou
BACKGROUND: The frequency of lactase persistence varies greatly among different populations. The T-13910 locus of the lactase gene is closely related to the persistence of lactase in European populations, but not in African populations and Northern China.
Objective: To investigate the allele T-13910 of lactase gene in Hangzhou urban population and the correlation between the single nucleotide polymorphism of adjacent genes and the persistence of lactase.
Methods: Adults without organic diseases in Hangzhou were examined by lactose hydrogen breath test to determine whether they were lactase persistent or lactase non-persistent. Peripheral blood was extracted for whole blood DNA extraction, PCR amplification and sequencing. The results of DNA sequencing were compared and analyzed to determine the T-13910 allele.
【学位授予单位】:浙江大学
【学位级别】:博士
【学位授予年份】:2009
【分类号】:R57;R181.3

【引证文献】

相关博士学位论文 前1条

1 杨建锋;乳糖摄入在腹泻型肠易激综合征发病中的作用及机制研究[D];浙江大学;2011年



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