بررسی بیان ژن CYFIP1 در خون بند ناف نوزادان و ارتباط آن با شاخص توده بدنی مادر

نوع مقاله : اصیل پژوهشی

نویسندگان

1 دانشجوی دکترای تخصصی بیوشیمی، گروه بیوشیمی، دانشکده پزشکی، دانشگاه علوم پزشکی زنجان، زنجان، ایران. دانشکده علوم زیستی، دانشگاه تربیت مدرس، تهران، ایران.

2 استادیار گروه زنان و مامایی، دانشکده پزشکی، دانشگاه علوم پزشکی زنجان، زنجان، ایران. مرکز تحقیقات بیماری‌های متابولیک زنجان، زنجان، ایران.

3 استادیار گروه آناتومی، دانشکده پزشکی، دانشگاه علوم پزشکی ایران، تهران، ایران.

4 کارشناس ارشد گروه بیوشیمی، دانشکده پزشکی، دانشگاه علوم پزشکی زنجان، زنجان، ایران.

5 کارشناس گروه زیست‌شناسی، دانشکده علوم پایه، دانشگاه مراغه، مراغه، ایران.

6 استاد گروه اطفال، دانشکده پزشکی، دانشگاه علوم پزشکی زنجان، زنجان، ایران.

7 استاد گروه بیوشیمی، مرکز تحقیقات بیماری‌های متابولیک زنجان، دانشگاه علوم پزشکی زنجان، زنجان، ایران.

10.22038/ijogi.2024.75355.5877

چکیده

مقدمه: مطالعه حاضر با هدف بررسی بیان ژن CYFIP1 در خون بند ناف (UCB) نوزادان و ارتباط احتمالی آن با دسته‌های مختلف شاخص ‌توده ‌بدنی مادر قبل از بارداری، پروفایل لیپیدی، وزن هنگام تولد و وضعیت نوزاد برای سن حاملگی انجام شد.
روش‌کار: این مطالعه مقطعی، از سال 1399 تا 1400 بر روی خون بند ناف 118 نوزاد پسر از بیمارستان موسوی و بیمارستان بهمن شهر زنجان انجام گرفت. زنان بر اساس BMI قبل از بارداری به سه گروه شاخص توده بدنی طبیعی، دارای اضافه وزن و چاق تقسیم شدند. هر نمونه UCB به دو قسمت تقسیم گردید. بخشی جهت بررسی پروفایل لیپیدی شامل لیپوپروتئین‌ با چگالی‌ کم، تری‌گلیسیرید، کلسترول ‌تام و لیپوپروتئین ‌با چگالی ‌بالا استفاده گردید. استخراج mRNA سلول‌های تک‌هسته‌ای خون محیطی جهت بررسی بیان ژن  CYFIP1انجام گردید. تجزیه و تحلیل داده‌ها با استفاده از نرم‌افزار آماری SPSS (نسخه 21) و آزمون همبستگی پیرسون انجام شد. میزان p کمتر از 05/0 معنی‌دار در نظر گرفته شد.
یافته ­ها: بیان ژن CYFIP1 در خون بند ناف نوزادان مادران دارای اضافه‌وزن و چاق بیشتر از زنان با وزن طبیعی بود (001/0=p). در UCB مادران در رده چاق، سطوح کلسترول و LDL نسبت به مادران با وزن ‌طبیعی و اضافه ‌وزن افزایش معنی‌داری نشان داد (001/0=p). همبستگی مثبتی بین BMI مادر قبل از بارداری و بیان ژن CYFIP1 خون بند ناف (333/0=r، 0001/0=p)، کلسترول (520/0=r، 0001/0=p)، تری‌گلیسیرید (290/0=r، 001/0=p)، سطح LDL (397/0=r، 0001/0=p) و وزن نوزاد در هنگام تولد بر اساس جنس و سن حاملگی (262/0=r، 001/0=p) وجود داشت.
نتیجه­ گیری: افزایش بیان ژن CYFIP1 در گروه­های مختلف BMI قبل از بارداری مادر و پروفایل لیپیدی همبستگی مثبت دارد که نشان می‌دهد عوامل خطری که در افزایش BMI نقش دارند، با توجه به نقش ژن CYFIP1 در تکامل مغز، ممکن است بتواند پیامدهای منفی بر سلامت و رشد جنین ایجاد کنند. 

کلیدواژه‌ها

موضوعات

عنوان مقاله [English]

CYFIP1 gene expression in umbilical cord blood and its relationship with maternal body mass index

نویسندگان [English]

  • Mahsa Eskandari 1
  • Elham Hosseini 2
  • Zahra Zandieh 3
  • Ehsan Noori 4
  • Raheleh Kafaeinezhad 5
  • Mansour Sadeghzadeh 6
  • Ali Awsat Mellati 7
1 PhD Student, Department of Biochemistry, Faculty of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran. School of Biological Sciences, Tarbiat Modares University, Tehran, Iran.
2 Assistant Professor, Department of Obstetrics and Gynecology, Faculty of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran. Zanjan Metabolic Diseases Research Center, Zanjan, Iran.
3 Assistant Professor, Department of Anatomy, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran.
4 M.Sc. of Biochemistry, Faculty of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran.
5 B.Sc. of Biology, School of Basic Sciences, University of Maragheh, Maragheh, Iran.
6 Professor, Department of Pediatrics, Faculty of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran.
7 Professor, Department of Biochemistry, Zanjan Metabolic Diseases Research Center, Zanjan University of Medical Sciences, Zanjan, Iran.
چکیده [English]

Introduction: The present study was conducted with aim to investigate the expression of the CYFIP1 gene in the umbilical cord blood (UCB) of newborns and its possible relationship with different categories of pre-pregnancy maternal body mass index (BMI), lipid profile, birth weight and infant status for gestational age.
Methods: This cross-sectional study was conducted from 2020 to 2021 on UCB of 118 male newborns from Mousavi and Bahman hospitals in Zanjan. According to pre-pregnancy BMI, women were divided into three groups: normal, overweight and obese. Each UCB sample was divided into two parts. A part was used to analyze the lipid profile including low-density lipoprotein (LDL), triglyceride (TG), total cholesterol (TC) and high-density lipoprotein (HDL). mRNA extraction of peripheral blood mononuclear cells was performed to investigate the expression of CYFIP1 gene. Data were analyzed using SPSS statistical software (version 21) and Pearson's correlation test. P<0.05 was considered statistically significant.
Results: The expression of the CYFIP1 gene was elevated in UCB from women classified as overweight or obese compared to those with normal weight (p=0.001). UCB of obese women exhibited higher cholesterol and LDL levels compared to normal-weight and overweight women (p=0.001). Positive correlations were observed between pre-pregnancy maternal BMI and cord blood CYFIP1 gene expression (r=0.333, p=0.0001), as well as cholesterol (r=0.520, p=0.0001), TG (r=0.290, p=0.001), LDL (r=0.397, p=0.0001), and birth weight of infants categorized based on gender and gestational age (r=0.262, p=0.001).
Conclusion: Increased expression of CYFIP1 gene is correlated positively with different categories of pre-pregnancy BMI and lipid profile, implying that regarding the role of CYFIP1 gene in brain development, the risk factors contributing to increasing BMI may have negative consequences on fetal health and development.

کلیدواژه‌ها [English]

  • Autism spectrum disorder
  • Body mass index
  • Cytoplasmic FMR1 interacting protein 1
  • CYFIP1

مراجع

  1. Maenner MJ. Prevalence of autism spectrum disorder among children aged 8 years—autism and developmental disabilities monitoring network, 11 sites, United States, 2016. MMWR. Surveillance Summaries 2020; 69.
  2. Loomes R, Hull L, Mandy WP. What is the male-to-female ratio in autism spectrum disorder? A systematic review and meta-analysis. Journal of the American Academy of Child & Adolescent Psychiatry 2017; 56(6):466-74.
  3. Baghdadli A, Picot MC, Pascal C, Pry R, Aussilloux C. Relationship between age of recognition of first disturbances and severity in young children with autism. European child & adolescent psychiatry 2003; 12:122-7.
  4. Lyall K, Schmidt RJ, Hertz-Picciotto I. Maternal lifestyle and environmental risk factors for autism spectrum disorders. International journal of epidemiology 2014; 43(2):443-64.
  5. Emberti Gialloreti L, Mazzone L, Benvenuto A, Fasano A, Garcia Alcon A, Kraneveld A, et al. Risk and protective environmental factors associated with autism spectrum disorder: evidence-based principles and recommendations. Journal of clinical medicine 2019; 8(2):217.
  6. Zahedi AF, Akouchekian M. The Effects of Environmental Factors and Immune Deficiency in the Etiology of Autistic Behavior. Razi Journal of Medical Sciences 2017; 23(153):26-34.
  7. Jiang CC, Lin LS, Long S, Ke XY, Fukunaga K, Lu YM, et al. Signalling pathways in autism spectrum disorder: mechanisms and therapeutic implications. Signal transduction and targeted therapy 2022; 7(1):229.
  8. Mandy W, Lai MC. Annual Research Review: The role of the environment in the developmental psychopathology of autism spectrum condition. Journal of Child Psychology and Psychiatry 2016; 57(3):271-92.
  9. Wang Y, Tang S, Xu S, Weng S, Liu Z. Maternal body mass index and risk of autism spectrum disorders in offspring: a meta-analysis. Scientific reports 2016; 6(1):34248.
  10. Getz KD, Anderka MT, Werler MM, Jick SS. Maternal Pre‐pregnancy Body Mass Index and Autism Spectrum Disorder among Offspring: A Population‐Based Case–Control Study. Paediatric and perinatal epidemiology 2016; 30(5):479-87.
  11. Andersen CH, Thomsen PH, Nohr EA, Lemcke S. Maternal body mass index before pregnancy as a risk factor for ADHD and autism in children. European child & adolescent psychiatry 2018; 27:139-48.
  12. Lyall K, Croen L, Daniels J, Fallin MD, Ladd-Acosta C, Lee BK, et al. The changing epidemiology of autism spectrum disorders. Annual review of public health 2017; 38:81-102.
  13. Oguro-Ando A, Rosensweig C, Herman E, Nishimura Y, Werling D, Bill BR, et al. Increased CYFIP1 dosage alters cellular and dendritic morphology and dysregulates mTOR. Molecular psychiatry 2015; 20(9):1069-78.
  14. Wang J, Tao Y, Song F, Sun Y, Ott J, Saffen D. Common regulatory variants of CYFIP1 contribute to susceptibility for autism spectrum disorder (ASD) and classical autism. Annals of human genetics 2015; 79(5):329-40.
  15. Kadakia R, Scholtens DM, Rouleau GW, Talbot O, Ilkayeva OR, George T, et al. Cord blood metabolites associated with newborn adiposity and hyperinsulinemia. The Journal of pediatrics 2018; 203:144-9.
  16. Cao T, Zhao J, Hong X, Wang G, Hu FB, Wang X, et al. Cord blood metabolome and BMI trajectory from birth to adolescence: a prospective birth cohort study on early life biomarkers of persistent obesity. Metabolites 2021; 11(11):739.
  17. Mordaunt CE, Park BY, Bakulski KM, Feinberg JI, Croen LA, Ladd-Acosta C, et al. A meta-analysis of two high-risk prospective cohort studies reveals autism-specific transcriptional changes to chromatin, autoimmune, and environmental response genes in umbilical cord blood. Molecular autism 2019; 10:1-21.
  18. Sealey LA, Hughes BW, Sriskanda AN, Guest JR, Gibson AD, Johnson-Williams L, et al. Environmental factors in the development of autism spectrum disorders. Environment international 2016; 88:288-98.
  19. Hinkle SN, Schieve LA, Stein AD, Swan DW, Ramakrishnan U, Sharma AJ. Associations between maternal prepregnancy body mass index and child neurodevelopment at 2 years of age. International journal of obesity 2012; 36(10):1312-9.
  20. Surén P, Gunnes N, Roth C, Bresnahan M, Hornig M, Hirtz D, et al. Parental obesity and risk of autism spectrum disorder. Pediatrics 2014; 133(5):e1128-38.
  21. van der Burg JW, Sen S, Chomitz VR, Seidell JC, Leviton A, Dammann O. The role of systemic inflammation linking maternal BMI to neurodevelopment in children. Pediatric research 2016; 79(1):3-12.
  22. Challier JC, Basu S, Bintein T, Minium J, Hotmire K, Catalano PM, et al. Obesity in pregnancy stimulates macrophage accumulation and inflammation in the placenta. Placenta 2008; 29(3):274-81.
  23. Chen X, Scholl TO. Oxidative stress: changes in pregnancy and with gestational diabetes mellitus. Current diabetes reports 2005; 5(4):282-8.
  24. Rowland J, Wilson CA. The association between gestational diabetes and ASD and ADHD: a systematic review and meta-analysis. Scientific reports 2021; 11(1):5136.
  25. Wells PG, McCallum GP, Chen CS, Henderson JT, Lee CJ, Perstin J, et al. Oxidative stress in developmental origins of disease: teratogenesis, neurodevelopmental deficits, and cancer. Toxicological sciences 2009; 108(1):4-18.
  26. Kong L, Norstedt G, Schalling M, Gissler M, Lavebratt C. The risk of offspring psychiatric disorders in the setting of maternal obesity and diabetes. Pediatrics 2018; 142(3).
  27. Fricano-Kugler C, Gordon A, Shin G, Gao K, Nguyen J, Berg J, et al. CYFIP1 overexpression increases fear response in mice but does not affect social or repetitive behavioral phenotypes. Molecular autism 2019; 10:1-16.
  28. Pagani M, Barsotti N, Bertero A, Trakoshis S, Ulysse L, Locarno A, et al. mTOR-related synaptic pathology causes autism spectrum disorder-associated functional hyperconnectivity. Nature communications 2021; 12(1):6084.
  29. Edlow AG, Hui L, Wick HC, Fried I, Bianchi DW. Assessing the fetal effects of maternal obesity via transcriptomic analysis of cord blood: a prospective case–control study. BJOG: An International Journal of Obstetrics & Gynaecology 2016; 123(2):180-9.
  30. Mordaunt CE, Jianu JM, Laufer BI, Zhu Y, Hwang H, Dunaway KW, et al. Cord blood DNA methylome in newborns later diagnosed with autism spectrum disorder reflects early dysregulation of neurodevelopmental and X-linked genes. Genome medicine 2020; 12:1-25.
  31. Mocarzel CC, Velarde GC, Antunes RD, Moreira de Sá RA, Kurjak A. Maternal obesity influences the endocrine cord blood profile of their offspring. Journal of perinatal medicine 2020; 48(3):242-8.
  32. Geraghty AA, Alberdi G, O’Sullivan EJ, O’Brien EC, Crosbie B, Twomey PJ, et al. Maternal and fetal blood lipid concentrations during pregnancy differ by maternal body mass index: findings from the ROLO study. BMC pregnancy and childbirth 2017; 17:1-7.
  33. Usui N, Iwata K, Miyachi T, Takagai S, Wakusawa K, Nara T, et al. VLDL-specific increases of fatty acids in autism spectrum disorder correlate with social interaction. EBioMedicine 2020; 58.
  34. Beaumont RN, Kotecha SJ, Wood AR, Knight BA, Sebert S, McCarthy MI, et al. Common maternal and fetal genetic variants show expected polygenic effects on risk of small-or large-for-gestational-age (SGA or LGA), except in the smallest 3% of babies. PLoS genetics 2020; 16(12):e1009191.
مجله زنان، مامایی و نازایی ایران
دوره 27، شماره 1
فروردین 1403
صفحه 31-45

فایل ها

هم رسانی

ارجاع به این مقاله

آمار