Abstract
Posttraumatic stress disorder (PTSD) and growth hormone secretagogue receptor (GHSR) were reported to be associated with plasma lipid and glucose levels. However, interplays of PTSD with GHSR on plasma lipid and glucose levels have not been explored yet. This study was to investigate the interplays of PTSD and GHSR rs495225 on plasma glucose and lipid profiles. A total of 709 high school students were recruited at 6 months after the 2008 Wenchuan earthquake. Variants of GHSR rs495225 were identified by polymerase chain reaction-restriction fragment length polymorphism analyses and verified by DNA sequencing. The PTSD Checklist Civilian Version (PCL-C) was used to assess PTSD. There was no significant difference of PTSD prevalence between the TT homozygotes and the C allele carriers. However, the students with PTSD had significantly lower levels of glucose, insulin and homeostasis model assessment of insulin resistance (HOMA-IR) than the students without PTSD in the C allele carriers of GHSR rs495225 after the adjustment for age, gender and body mass index (BMI), but higher levels of TG and TG/HDL-C in the TT homozygotes. Meanwhile, the TT homozygotes had lower levels of HDL-C than the C allele carriers in the students without PTSD, but higher levels of insulin and HOMA-IR in the subjects with PTSD. After the adjustment of age and gender, and additional adjustment for BMI, the results were not changed except the difference of insulin was only a tendency (p = 0.054) after the additional adjustment for BMI. PTSD may augment TG levels and the related lipid ratio TG/HDL-C in the TT homozygotes of GHSR rs495225 but decrease the levels of glucose, insulin and HOMA-IR in the C allele carriers.
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References
Baigent C et al (2005) Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet 366:1267–1278. https://doi.org/10.1016/s0140-6736(05)67394-1
Barber J, Bayer L, Pietrzak RH, Sanders KA (2011) Assessment of rates of overweight and obesity and symptoms of posttraumatic stress disorder and depression in a sample of operation enduring freedom/operation Iraqi freedom veterans. Milit Med 176:151–155
Barnes VA, Treiber FA, Ludwig DA (2005) African-American adolescents' stress responses after the 9/11/01 terrorist attacks. J Adolesc Health 36:201–207. https://doi.org/10.1016/j.jadohealth.2004.02.035
Beiras-Fernandez A et al (2010) Altered myocardial expression of ghrelin and its receptor (GHSR-1a) in patients with severe heart failure. Peptides 31:2222–2228. https://doi.org/10.1016/j.peptides.2010.08.019
Bijari B, Taheri F, Chahkandi T, Kazemi T, Namakin K, Zardast M (2015) The relationship between serum lipids and obesity among elementary school in Birjand: a case control study. J Res Health Sci 15:83–87
Blanchard EB, Jones-Alexander J, Buckley TC, Forneris CA (1996) Psychometric properties of the PTSD Checklist (PCL). Behav Res Therapy 34:669–673
Calderoni ME, Alderman EM, Silver EJ, Bauman LJ (2006) The mental health impact of 9/11 on inner-city high school students 20 miles north of Ground Zero. The Journal of adolescent health 39:57–65. https://doi.org/10.1016/j.jadohealth.2005.08.012
Cook JM, Elhai JD, Arean PA (2005) Psychometric properties of the PTSD Checklist with older primary care patients. J Trauma Stress 18:371–376. https://doi.org/10.1002/jts.20038
Date Y et al (2002) Ghrelin is present in pancreatic alpha-cells of humans and rats and stimulates insulin secretion. Diabetes 51:124–129
Dedert EA, Calhoun PS, Watkins LL, Sherwood A, Beckham JC (2010) Posttraumatic stress disorder, cardiovascular, and metabolic disease: a review of the evidence. Ann Behav Med 39:61–78. https://doi.org/10.1007/s12160-010-9165-9
Dobie DJ, Kivlahan DR, Maynard C, Bush KR, Davis TM, Bradley KA (2004) Posttraumatic stress disorder in female veterans: association with self-reported health problems and functional impairment. Arch Intern Med 164:394–400. https://doi.org/10.1001/archinte.164.4.394
Galea S, Nandi A, Vlahov D (2005) The epidemiology of post-traumatic stress disorder after disasters. Epidemiol Rev 27:78–91. https://doi.org/10.1093/epirev/mxi003
Goodwin RD, Davidson JR (2005) Self-reported diabetes and posttraumatic stress disorder among adults in the community. Prev Med 40:570–574
Guzzaloni G, Moreni G, Ardizzi A, Moro D, Grugni G, Morabito F (1991) Correlation between lipid pattern and body mass index in obesity. Minerva Med 82:339–344
Hosoda H, Kojima M, Kangawa K (2006) Biological, physiological, and pharmacological aspects of ghrelin. J Pharmacol Sci 100:398–410
Howard AD et al (1996) A receptor in pituitary and hypothalamus that functions in growth hormone release. Science (New York, NY) 273:974–977
Hsia SH, Pan D, Berookim P, Lee ML (2006) A population-based, cross-sectional comparison of lipid-related indexes for symptoms of atherosclerotic disease. Am J Cardiol 98:1047–1052. https://doi.org/10.1016/j.amjcard.2006.05.024
Iii JL, Hahn H, Martin A (2006) 9/11: mental health in the wake of terrorist attacks. BMJ 333:219
Jendricko T, Vidović A, Grubisić-Ilić M, Romić Z, Kovacić Z, Kozarić-Kovacić D (2009) Homocysteine and serum lipids concentration in male war veterans with posttraumatic stress disorder. Prog Neuropsychopharmacol Biol Psychiatr 33:134–140
Jiang H, Betancourt L, Smith RG (2006) Ghrelin amplifies dopamine signaling by cross talk involving formation of growth hormone secretagogue receptor/dopamine receptor subtype 1 heterodimers. Molecular endocrinology (Baltimore, Md) 20:1772–1785. https://doi.org/10.1210/me.2005-0084
Kagan BL, Leskin G, Haas B, Wilkins J, Foy D (1999) Elevated lipid levels in Vietnam veterans with chronic posttraumatic stress disorder. Biol Psychiatr 45:374–377
Karlović D, Buljan D, Martinac M, Marcinko D (2004) Serum lipid concentrations in Croatian veterans with post-traumatic stress disorder, post-traumatic stress disorder comorbid with major depressive disorder, or major depressive disorder. J Korean Med Sci 19:431–436
Karlovic D, Martinac M, Buljan D, Zoricic Z (2004) Relationship between serum lipid concentrations and posttraumatic stress disorder symptoms in soldiers with combat experiences. Acta Med Okayama 58:23–27
Kozaric-Kovacic D, Ilic MG, Romic Z, Vidovic A, Jendricko T, Pivac N (2009) Body mass index in male Caucasian veterans with or without posttraumatic stress disorder Prog Neuro-Psychopharmacol. Biol Psychiatr 33:1447–1450. https://doi.org/10.1016/j.pnpbp.2009.07.026
Kulkarni M, Pole N (2008) Psychiatric distress among Asian and European American Survivors of the 1994 Northridge Earthquake. J Nervous Mental Dis 196:597–604. https://doi.org/10.1097/NMD.0b013e3181813290
Liu B, Garcia EA, Korbonits M (2011) Genetic studies on the ghrelin, growth hormone secretagogue receptor (GHSR) and ghrelin O-acyl transferase (GOAT) genes. Peptides 32:2191–2207. https://doi.org/10.1016/j.peptides.2011.09.006
Liu ZY, Yang YF, Ye YL, Zeng ZQ, Xiang YJ, Yuan P (2010) One-year follow-up study of post-traumatic stress disorder among adolescents following the Wen-Chuan earthquake in China. Biosci Trends 4:96–102
Lukaschek K et al (2013) Relationship between posttraumatic stress disorder and Type 2 Diabetes in a population-based cross-sectional study with 2970 participants. J Psychosomat Res 74:340–345. https://doi.org/10.1016/j.jpsychores.2012.12.011
Mager U et al (2008) Variations in the ghrelin receptor gene associate with obesity and glucose metabolism in individuals with impaired glucose tolerance. PloS ONE 3:e2941. https://doi.org/10.1371/journal.pone.0002941
McNally RJ (2003) Progress and controversy in the study of posttraumatic stress disorder. Annu Rev Psychol 54:229–252. https://doi.org/10.1146/annurev.psych.54.101601.145112
Mihaylova B et al (2012) The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials. Lancet 380:581–590. https://doi.org/10.1016/s0140-6736(12)60367-5
Millan J et al (2009) Lipoprotein ratios: Physiological significance and clinical usefulness in cardiovascular prevention. Vasc Health Risk Manage 5:757–765
Pereira SMP, Power C (2013) Life course body mass index, birthweight and lipid levels in mid-adulthood: a nationwide birth cohort study. Eur Heart J 34:1215–1224. https://doi.org/10.1093/eurheartj/ehs333
Polac I, Stachowiak G, Jedrzejczyk S, Stetkiewics T, Sobieszczanska S, Pertynski T (2003) Hemostatic variables, carbohydrate metabolism and lipid profile in women with low body mass index. Gynecol Endocrinol 17:151–157
Shai I et al (2004) Multivariate assessment of lipid parameters as predictors of coronary heart disease among postmenopausal women: potential implications for clinical guidelines. Circulation 110:2824–2830. https://doi.org/10.1161/01.cir.0000146339.57154.9b
Shamai L et al (2011) Association of body mass index and lipid profiles: evaluation of a broad spectrum of body mass index patients including the morbidly obese. Obes Surg 21:42–47. https://doi.org/10.1007/s11695-010-0170-7
Sun Y, Wang P, Zheng H, Smith RG (2004) Ghrelin stimulation of growth hormone release and appetite is mediated through the growth hormone secretagogue receptor. Proc Natl Acad Sci USA 101:4679–4684. https://doi.org/10.1073/pnas.0305930101
Tochigi M et al (2002) Serum cholesterol, uric acid and cholinesterase in victims of the Tokyo subway sarin poisoning: a relation with post-traumatic stress disorder. Neurosci Res 44:267–272
Vancampfort D et al (2016) Type 2 diabetes among people with posttraumatic stress disorder: systematic review and meta-analysis. Psychosom Med 78:465–473. https://doi.org/10.1097/psy.0000000000000297
Vartiainen J, Poykko SM, Raisanen T, Kesaniemi YA, Ukkola O (2004) Sequencing analysis of the ghrelin receptor (growth hormone secretagogue receptor type 1a) gene. Eur J Endocrinol 150:457–463
Vieweg WV, Julius DA, Bates J, Quinn JF 3rd, Fernandez A, Hasnain M, Pandurangi AK (2007) Posttraumatic stress disorder as a risk factor for obesity among male military veterans. Acta Psychiatr Scand 116:483–487. https://doi.org/10.1111/j.1600-0447.2007.01071.x
Vilibić M, Jukić V, Pandžićsakoman M, Bilić P, Milošević M (2014) Association between total serum cholesterol and depression, aggression, and suicidal ideations in war veterans with posttraumatic stress disorder: a cross-sectional study. Croat Med J 55:520–529
Wahlström L, Michélsen H, Schulman A, Backheden M (2009) Psychological distress and sick leave in Swedish survivors of the 2004 tsunami: a comparison with a population sample. J Nerv Ment Dis 922:918. https://doi.org/10.1097/NMD.0b013e3181c29a60
Wakabayashi I (2014) Influence of age and gender on lipid accumulation product and its relation to diabetes mellitus in Japanese. Clin Chim Acta 431:221–226. https://doi.org/10.1016/j.cca.2014.02.002
Wang HJ et al (2004) Ghrelin receptor gene: identification of several sequence variants in extremely obese children and adolescents, healthy normal-weight and underweight students, and children with short normal stature. J Clin Endocrinol Metabol 89:157–162. https://doi.org/10.1210/jc.2003-031395
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We acknowledge Mei Fan for her technical supports.
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This study was supported by the Program of Sichuan Province for International Cooperation and Exchanges of Sciences and Technologies (Grant no. 2017HH0074).
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Ding Zhi Fang was responsible for conception, study design, data interpretation and manuscript finalization. Mi Su was responsible for lab experiments, statistical analysis and manuscript preparation. Yan Jun Si and Qi Wei Guo were involved in lab experiments and statistical analysis. Mei Yang, Xu Chen and Jia Lin were involved in evolving the ideas and revising the manuscript. All authors have contributed to and have approved the final manuscript.
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This study was supported by the Program of Sichuan Province for International Cooperation and Exchanges of Sciences and Technologies (Grant no. 2017HH0074). Professor Ding Zhi Fang is the recipient of the grant.
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Su, M., Si, Y.J., Guo, Q.W. et al. Posttraumatic Stress Disorder Augments Plasma Triglycerides in TT Homozygotes of rs495225 at Growth Hormone Secretagogue Receptor Gene. Biochem Genet 57, 273–288 (2019). https://doi.org/10.1007/s10528-018-9890-5
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DOI: https://doi.org/10.1007/s10528-018-9890-5