Association of APOE gene polymorphisms and multiple risk factors with hypertension in middle-aged and elderly Tibetan population in Tibet on Bayesian network model

BACKGROUND The distribution of Apolipoprotein E (APOE) gene and its relationship with hypertension at high altitude in Tibet have not been elucidated. The purpose of this study was to understand the distribution of APOE genotypes and APOE rs7412, rs429358 genotypes in the middle-aged and elderly Tibetan population in Tibet, and to explore the related influencing factors by constructing a Bayesian network model of hypertension in middle-aged and elderly Tibetans.

From November 2021 to November 2022, a multi-stage cluster random sampling method was employed to collect data from 511 middle-aged and elderly Tibetans residing in the Ali region, Nagqu City, and Shannan City of Tibet. The APOE gene, rs429358 and rs7412 single nucleotide polymorphisms (SNPs) were analyzed by fluorescence polymerase chain reaction (PCR). Multivariate logistic regression analysis and Bayesian Network (BN) were applied to examine the relationship between Covariates and hypertension.

Among all subjects, the frequencies of genotypes ε2/ε3, ε2/ε4, ε3/ε3 and ε3/ε4 were 14.8%,1.8%,75.0%, and 8.4%, respectively. APOE gene rs7412 locus CC, CT and TT genotype frequencies were 83.4%, 0 and 16.6%, respectively, and rs429358 locus TT, TC and CC genotypes, genotype frequencies were 89.8%, 10.2% and 0. The results of this study indicated no correlation between APOE genotypes, APOE rs7412, rs429358 genotypes, and the prevalence of hypertension in middle-aged and elderly Tibetan population in Tibet. Sex, age, overweight obesity, hyperhomocysteinemia (HHcy) and High Altitude Pulmonary Edema (HAPC) represent direct risk factors for hypertension based on a Bayesian network.

APOE genotype and APOE rs7412, rs429358 genotypes were not genetically correlated with hypertension in middle-aged and elderly Tibetan populations in Tibet. The Bayesian network model revealed the direct and indirect factors and the strength of the association of the hypertension. Additionally, it elucidated the complex network relationships among these factors, which provided a scientific basis for the early prevention of hypertension among middle-aged and elderly Tibetan populations in Tibet. Competing Interest Statement The authors have declared no competing interest. Funding Statement This study was supported by the Tibet Autonomous Region Research Funding (grants 18080273 and 00061243). Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The survey was reviewed and approved by the Medical Ethics Committee of Tibet University I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data Availability The datasets that support the findings of this study are available from Medical College of Tibet University but are restricted to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission of Medical College of Tibet University. If someone wants to request data from this study, please contact the corresponding author. Non-standard Abbreviations and Acronyms - HTN - hypertension - SBP - systolic blood pressure - DBP - diastolic blood pressure - UA - Blood uric acid - TC - total cholesterol - TG - triglycerides - LDL-C - low-density lipoprotein cholesterol - HDL-C - high-density lipoprotein cholesterol - FBG - fasting blood glucose - Hcy - homocysteine - HHcy - hyperhomocysteinemia - BMI - Body Mass Index - HAPC - High Altitude Pulmonary Edema - OR - Odds ratio - CI - Confidence interval