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Differential Expression of HERV-W in Peripheral Blood in Multiple Sclerosis and Healthy Patients in Two Different Ethnic Groups.

ABSTRACT: Overexpression of the Human endogenous retrovirus W (HERV-W) group of inherited retroviruses has been consistently linked with Multiple Sclerosis (MS). However most of the studies on this link have focused on European genetic groups with a very high risk of MS and it is not clear that this relationship holds for all ethnic groups. This study examined via qPCR the RNA expression in peripheral blood of HERV-W (the multiple sclerosis associated retrovirus variant MSRV) of MS patients and healthy controls from two ethnic groups with very different risk rates of MS. Population one was derived from the UK with a Northern European genetic background and an MS risk rate of 108/100,000, population two was derived from the republic of Tatarstan, Russian Federation, with a mixed Russian (Eastern European) and Tartar (Turkic or Volga/Urals) population with an MS risk rate of 21-31/100,000. The Russian population displayed a significantly higher basal level of expression of MSRV in both healthy and MS individuals when compared to the British control population with a trend in the Russian population towards higher expression levels in MS patients than healthy patients.

SUBMITTER: Tarlinton R

PROVIDER: S-EPMC7002920 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionPeople of South Asian, African-Caribbean and Irish ethnicity are known to have worse cardiovascular outcomes than those from the white British group. While the reasons underpinning this are complex, the effect of hypertension is both significant and modifiable. In recent years, there has been increasing interest in and uptake of 'out-of-office' methods for blood pressure (BP) monitoring. However, guidance in this area has been largely based on research among the white population. This study aims to answer the following questions: (1) How often and in what ways does blood pressure (BP) monitoring occur and how does this differ between white and the above minority ethnic populations. (2) Are the thresholds for diagnosis of hypertension, and treatment targets in hypertension comparable for white British and minority ethnic populations using different measurement modalities: office blood pressure, ambulatory BP monitoring and home monitoring? (3) What preferences for BP measurement do people from white and minority ethnic populations have?Methods and analysisA mixed methods approach will be used including the following: (1) A postal survey sent to 8000 hypertensive and not-known-to-be-hypertensive people from all four ethnic groups will determine current patterns of BP monitoring. (2) A validation study will compare BP measurement by ambulatory monitoring with office standard measurement, office research measurement and home monitoring in 200 people from each of the ethnic groups concerned. (3) Focus groups organised by ethnicity and gender will gather qualitative data regarding patient preferences for and experiences of BP measurement in each of the given modalities. The data collected from these phases will be analysed appropriately in order to answer the above research questions.Ethics and disseminationEthical approval has been gained from the Black Country Research Ethics Committee: Ref 09/H1202/114. The results of this work will be disseminated via journal publication and conference presentation.

Project description:Background and objectivesMultiple sclerosis (MS) is a chronic, progressive neurological disease characterized by early-stage neuroinflammation, neurodegeneration, and demyelination that involves a spectrum of heterogeneous clinical manifestations in terms of disease course and response to therapy. Even though several disease-modifying therapies (DMTs) are available to prevent MS-related brain damage-acting on the peripheral immune system with an indirect effect on MS lesions-individualizing therapy according to disease characteristics and prognostic factors is still an unmet need. Given that deregulated miRNAs have been proposed as diagnostic tools in neurodegenerative/neuroinflammatory diseases such as MS, we aimed to explore miRNA profiles as potential classifiers of the relapsing-remitting MS (RRMS) patients' prospects to gain a more effective DMT choice and achieve a preferential drug response.MethodsA total of 25 adult patients with RRMS were enrolled in a cohort study, according to the latest McDonald criteria before (pre-cladribine, pre-CLA; pre-ocrelizumab, pre-OCRE, time T0) and after high-efficacy DMTs, time T1, 6 months post-CLA (n = 10, 7 F and 3 M, age 39.0 ± 7.5) or post-OCRE (n = 15, 10 F and 5 M, age 40.5 ± 10.4) treatment. A total of 15 age- and sex-matched healthy control subjects (9 F and 6 M, age 36.3 ± 3.0) were also selected. By using Agilent microarrays, we analyzed miRNA profiles from peripheral blood mononuclear cells (PBMC). miRNA-target networks were obtained by miRTargetLink, and Pearson's correlation served to estimate the association between miRNAs and outcome clinical features.ResultsFirst, the miRNA profiles of pre-CLA or pre-OCRE RRMS patients compared to healthy controls identified modulated miRNA patterns (40 and seven miRNAs, respectively). A direct comparison of the two pre-treatment groups at T0 and T1 revealed more pro-inflammatory patterns in the pre-CLA miRNA profiles. Moreover, both DMTs emerged as being capable of reverting some dysregulated miRNAs toward a protective phenotype. Both drug-dependent miRNA profiles and specific miRNAs, such as miR-199a-3p, miR-29b-3p, and miR-151a-3p, emerged as potentially involved in these drug-induced mechanisms. This enabled the selection of miRNAs correlated to clinical features and the related miRNA-mRNA network.DiscussionThese data support the hypothesis of specific deregulated miRNAs as putative biomarkers in RRMS patients' stratification and DMT drug response.

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Differential Expression of HERV-W in Peripheral Blood in Multiple Sclerosis and Healthy Patients in Two Different Ethnic Groups.

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