ABCA1、AGT基因和职业紧张交互作用与高血压的关系
Relationship of hypertension with interactions among ABCA1 gene, AGT gene, and occupational stress
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摘要:
背景 高血压是基因与环境共同作用导致的疾病。目前关于职业紧张、ATP结合盒转运体A1基因(
ABCA1 )和血管紧张素原基因(AGT )多态性与高血压关系的研究多为关注单基因或单环境影响。目的 探讨
ABCA1 和AGT 基因位点多态性和职业紧张交互作用与高血压患病的关系。方法 将2018年课题组在克拉玛依油田工人中采用随机整群抽样方法调查的1200人中的198例高血压患者作为病例,按照性别、年龄(±3岁)和民族1∶1匹配的原则选择相应的对照组,剔除血样、问卷或DNA纯(浓)度不达标者,最终确定病例组和对照组均为153人。运用调查问卷收集油田工人的一般信息,并通过修订版的职业紧张量表(OSI-R)进行职业紧张程度的评价。运用聚合酶链式反应限制性片段长度多态性技术检测
ABCA1 V825I 、R219K 位点和AGT M235T 、T174M 位点的基因型。采用广义多因子降维法分析ABCA1 和AGT 的基因-基因交互作用,以及基因-职业紧张的交互作用与高血压患病率的关系。结果 病例组和对照组职业紧张程度的分布差异具有统计学意义(
P =0.001),病例组的高度职业紧张检出率(65.4%)高于对照组(47.7%)。病例组和对照组的ABCA1 V825I 位点、R219K 位点,AGT M235T 位点基因型和等位基因的分布差异均有统计学意义(P <0.05)。条件logistic回归结果显示,ABCA1 V825I 位点VI 、II 基因型(OR VI =1.682,95%CI :1.099~2.573;OR II =1.708,95%CI :1.045~2.790)、AGT M235T 位点TT 基因型(OR =1.645,95%CI :1.022~2.647)、高度职业紧张(OR =2.642,95%CI :1.228~5.686)人群高血压患病风险更高(P <0.05);而ABCA1 R219K 位点和AGT T174M 位点多态性与高血压患病的关联无统计学意义(P >0.05)。ABCA1 V825I 、R219K 位点与AGT M235T 位点之间的基因-基因交互作用与高血压患病有关(训练集和测试集的精确度分别为0.68和0.63,交叉验证一致性系数为10/10,P <0.05),且ABCA1 V825I 与AGT M235T 位点呈正交互作用;ABCA1 V825I 、R219K 位点、AGT M235T 位点与职业紧张间的基因-环境交互作用与高血压患病有关(训练集和测试集精确度为0.74和0.63,交叉验证一致性系数为10/10,P <0.05),且AGT M235T 位点与职业紧张呈负交互作用。结论 ABCA1 V825I 位点VI 、II 基因型、AGT M235T 位点TT 基因型和高度职业紧张可能是克拉玛依油田工人高血压的危险因素,且ABCA1 、AGT 基因多态性和职业紧张三者之间的基因-基因、基因-环境的交互作用与高血压患病有关。Abstract:Background Hypertension is influenced by both genes and environment. At present, most studies on the relationship among occupational stress, polymorphisms of ATP binding cassette subfamily A member 1 (
ABCA1 ) or angiotensinogen (AGT ) genes, and hypertension focus on single gene or single environmental effects.Objective To investigate the relationship of potential interactions between
ABCA1 andAGT gene polymorphisms and occupational stress with the prevalence of hypertension.Methods A total of 198 hypertensive patients were selected as the case group from the 1200 oilfield workers in Karamay Oilfield in 2018 with random cluster sampling method, and the control group was selected as 1∶1 matched subjects for sex, age (±3 years), and ethnicity, after excluding blood samples, questionnaires, or DNA purity (concentration) that did not meet the inclusion criteria. Finally, 153 workers in the hypertension case group and 153 workers in the control group were determined. A questionnaire was used to collect general information of the oilfield workers, and the Occupational Stress Inventory Revised Edition (OSI-R) was used to evaluate occupational stress. Polymerase chain reaction-restriction fragment length polymorphism technology was used to detect the genotypes of
V825I andR219K loci ofABCA1 as well asM235T andT174M loci ofAGT . The gene-gene interaction ofABCA1 andAGT and the relationship between the interaction of gene-occupational stress and the prevalence of hypertension were analyzed by generalized multi-factor dimensionality reduction method.Results The difference of reported occupational stress between the hypertension case group and the control group was statistically significant (
P =0.001), and the reporting rate of high occupational stress in the case group (65.4%) was higher than that in the control group (47.7%). The genotype and allele distributions ofABCA1 V825I ,ABCA1 R219K , andAGT M235T between the hypertension case group and the control group were significantly different (P <0.05). The results of conditional logistic regression analysis showed thatVI andII genotypes atV825I locus ofABCA1 (OR VI =1.682, 95%CI : 1.099-2.573;OR II =1.708, 95%CI : 1.045-2.790),TT genotype atM235T locus ofAGT (OR =1.645, 95%CI : 1.022-2.647), and high occupational stress (OR =2.642, 95%CI : 1.228-5.686) increased the risks for hypertension (P <0.05). There was no significant correlation betweenABCA1 R219K orAGT T174M polymorphisms and the prevalence of hypertension (P >0.05). The gene-gene interactions betweenABCA1 V825I andR219K loci andAGT M235T locus were associated with hypertension (accuracy on training and test sets was 0.68 and 0.63, respectively, with a cross-validation coefficient of 10/10,P <0.05), andABCA1 V825I locus positively interacted withAGT M235T locus. The gene-environment interactions amongABCA1 V825I andR219K loci,AGT M235T locus, and occupational stress were associated with hypertension (accuracy on training and test sets was 0.74 and 0.63, respectively, with a cross-validation coefficient of 10/10,P <0.05), andAGT M235T locus negatively interacted with occupational stress.Conclusion Genotype
VI andII ofV825I locus atABCA1, genotypeTT ofM235T locus atAGT , and high occupational stress may be risk factors for oilfield workers’ hypertension in Karamay, and the interactions of gene-gene and gene-environment amongABCA1 andAGT gene polymorphisms and occupational stress may be associated with hypertension.