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      Interaction between mitochondrial NADH dehydrogenase subunit-2 5178 C > A and clinical risk factors on the susceptibility of essential hypertension in Chinese population

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          Abstract

          Background

          The mitochondrial genotype 5178 cytosine/adenine (5178 C > A) within the NADH dehydrogenase subunit-2 gene (ND2) was proved to associate with longevity and predispose resistance to adult-onset diseases. This study aimed to confirm the interactive effects between ND 25178 C > A and clinical risk factors on the susceptibility of essential hypertension in Chinese general population.

          Materials and Methods

          The relationship between the ND2 5178 C > A variation and the risk of hypertension was investigated in 817 hypertensives and 821 matched normotensives. The interactive effects between ND2 5178 C > A and clinical risk factors were evaluated.

          Results

          The ND2 5178 A allele was more frequent in normotensives than in hypertensives (32.64% vs. 24.24%; adjusted OR: 0.62, 95% CI: 0.49–0.79, P = 1.3 × 10 − 4). After stratification, the significant association between ND2 5178 C > A and hypertension was found only in current smokers (OR: 0.44, 95% CI: 0.31–0.62), but not in non-current smokers ( p <  0.01 for interaction). Smoking status (OR: 1.51, 95% CI: 1.11–2.06) and high triglycerides (OR: 1.57, 95% CI: 1.10–2.24) were found independently associated with hypertension only in carriers of 5178 C allele but not in carriers of 5178 A allele.

          Conclusions

          In conclusion, ND2 5178 A allele could confer a lower risk for essential hypertension in Chinese by the interaction with smoking status. The higher risk of hypertension imposed by smoking and high TG may be altered by ND2 5178 A allele.

          Electronic supplementary material

          The online version of this article (10.1186/s12881-019-0838-3) contains supplementary material, which is available to authorized users.

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          Most cited references29

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          Adult Current Smoking: Differences in Definitions and Prevalence Estimates—NHIS and NSDUH, 2008

          Objectives. To compare prevalence estimates and assess issues related to the measurement of adult cigarette smoking in the National Health Interview Survey (NHIS) and the National Survey on Drug Use and Health (NSDUH). Methods. 2008 data on current cigarette smoking and current daily cigarette smoking among adults ≥18 years were compared. The standard NHIS current smoking definition, which screens for lifetime smoking ≥100 cigarettes, was used. For NSDUH, both the standard current smoking definition, which does not screen, and a modified definition applying the NHIS current smoking definition (i.e., with screen) were used. Results. NSDUH consistently yielded higher current cigarette smoking estimates than NHIS and lower daily smoking estimates. However, with use of the modified NSDUH current smoking definition, a notable number of subpopulation estimates became comparable between surveys. Younger adults and racial/ethnic minorities were most impacted by the lifetime smoking screen, with Hispanics being the most sensitive to differences in smoking variable definitions among all subgroups. Conclusions. Differences in current cigarette smoking definitions appear to have a greater impact on smoking estimates in some sub-populations than others. Survey mode differences may also limit intersurvey comparisons and trend analyses. Investigators are cautioned to use data most appropriate for their specific research questions.
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            Mitochondrial genotype associated with longevity.

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              Maternally inherited essential hypertension is associated with the novel 4263A>G mutation in the mitochondrial tRNAIle gene in a large Han Chinese family.

              Despite maternal transmission of hypertension in some pedigrees, pathophysiology of maternally inherited hypertension remains poorly understood. To establish a causative link between mitochondrial dysfunction and essential hypertension. A total of 106 subjects from a large Chinese family underwent clinical, genetic, molecular, and biochemical evaluations. Fifteen of 24 adult matrilineal relatives exhibited a wide range of severity in essential hypertension, whereas none of the offspring of affected fathers had hypertension. The age at onset of hypertension in the maternal kindred varied from 20 years to 69 years, with an average of 44 years. Mutational analysis of their mitochondrial genomes identified a novel homoplasmic 4263A>G mutation located at the processing site for the tRNA(Ile) 5'-end precursor. An in vitro processing analysis showed that the 4263A>G mutation reduced the efficiency of the tRNA(Ile) precursor 5'-end cleavage catalyzed by RNase P. tRNA Northern analysis revealed that the 4263A>G mutation caused ≈46% reduction in the steady-state level of tRNA(Ile). An in vivo protein-labeling analysis showed ≈32% reduction in the rate of mitochondrial translation in cells carrying the 4263A>G mutation. Impaired mitochondrial translation is apparently a primary contributor to the reductions in the rate of overall respiratory capacity, malate/glutamate-promoted respiration, succinate/glycerol-3-phosphate-promoted respiration, or N,N,N',N'-tetramethyl-p-phenylenediamine/ascorbate-promoted respiration and the increasing level of reactive oxygen species in cells carrying the 4263A>G mutation. These data provide direct evidence that mitochondrial dysfunction caused by mitochondrial tRNA(Ile) 4263A>G mutation is involved in essential hypertension. Our findings may provide new insights into pathophysiology of maternally transmitted hypertension.
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                Author and article information

                Contributors
                cx2263@163.com
                he_xy@yahoo.com
                zhuchaodoctor@163.com
                ZhangYS301@163.com
                LiZB_301@163.com
                LiuYQ_301@163.com
                ZhangYX_301@163.com
                yintong2000@yahoo.com
                liyangfjs@163.com
                Journal
                BMC Med Genet
                BMC Med. Genet
                BMC Medical Genetics
                BioMed Central (London )
                1471-2350
                5 July 2019
                5 July 2019
                2019
                : 20
                : 121
                Affiliations
                [1 ]GRID grid.452206.7, Department of Geriatrics, , The First Affiliated Hospital of Chongqing Medical University, ; Chongqing, China
                [2 ]ISNI 0000 0004 1761 8894, GRID grid.414252.4, Department of Cardiology, , General Hospital of Chinese People’s Liberation Army, ; No.28 Fu Xing Road, Beijing, 100853 China
                [3 ]Department of Ophthalmology, 958 Hospital of PLA ARMY, Chongqing, China
                [4 ]ISNI 0000 0004 0369 153X, GRID grid.24696.3f, Department of Cardiology, , Beijing Friendship Hospital, Capital Medical University, ; Beijing, China
                Author information
                http://orcid.org/0000-0001-5432-0729
                Article
                838
                10.1186/s12881-019-0838-3
                6612147
                31277597
                611fee98-8e6a-4918-a9f9-8be567d8732c
                © The Author(s). 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 16 January 2019
                : 31 May 2019
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 81870249
                Award Recipient :
                Funded by: National Key RD Program of China
                Award ID: 2017YFC0908700
                Award ID: 2017YFC0908703
                Award Recipient :
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2019

                Genetics
                hypertension,mitochondria,nadh dehydrogenase subunit 2,variation,interaction
                Genetics
                hypertension, mitochondria, nadh dehydrogenase subunit 2, variation, interaction

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