AI Chat Paper
Note: Please note that the following content is generated by AMiner AI. SciOpen does not take any responsibility related to this content.
{{lang === 'zh_CN' ? '文章概述' : 'Summary'}}
{{lang === 'en_US' ? '中' : 'Eng'}}
Chat more with AI
Powered by AMiner. Clicking this button will take you away from SciOpen.
Home Genes & Diseases Article
PDF (292.6 KB)
Cite
EndNote(RIS) BibTeX
Collect
Submit Manuscript AI Chat Paper
Show Outline
Outline
Show full outline
Hide outline
Outline
Show full outline
Hide outline
Full Length Article | Open Access

Maternal vitamin D level and vitamin D receptor gene polymorphism as a risk factor for congenital heart diseases in offspring; An Egyptian case-control study

Wesam A. Mokhtara,( ), Amal Fawzyb, Reem M. Allamc, Rania M. Amerd, Mona S. Hamede
Pediatric Department, Faculty of Medicine, Zagazig University, Egypt
Medical Biochemistry Department, Faculty of Medicine, Zagazig University, Egypt
Clinical Pathology Department, Faculty of Medicine, Zagazig University, Egypt
Medical Microbiology and Immunology Department, Faculty of Medicine, Zagazig University, Egypt
Public Health and Community Medicine, Faculty of Medicine, Zagazig University, Egypt

Peer review under responsibility of Chongqing Medical University.

Show Author Information

Abstract

Vitamin D & vitamin D receptor (VDR) signaling play a very crucial role in early embryonic heart development. We construct this case-control study to investigate the association between maternal serum vitamin D level & VDR gene Fok1 polymorphism and risk of congenital heart defects (CHD) in offspring. Fifty mothers who had term neonates with CHD were considered as cases. Fifty age-comparable healthy mothers who had neonates without CHD were contemplated as controls. Maternal serum 25 hydroxyvitamin D [25(OH) D] level was tested using ELISA. Maternal VDR gene Fok1 polymorphism was analyzed using PCR-based RFLP-assay. There was a significant decrease in maternal vitamin D level (P = 0.002) and a significant increase in vitamin D deficient status (P = 0.007) among cases when compared to controls. VDR gene Fok1 genotypes distribution frequency were in accordance with Hardy Weinberg equilibrium (HW) among controls. A significant increase in VDR gene Fok1 F/f & f/f genotypes and f allele were observed in cases compared to controls with estimated odds ratio (95% confidence interval) & P-value of 3 (1–8) & P = 0.006, 11 (1–97) & P = 0.01 and 3 (2–6) & P = 0.001 respectively. There was a significant decrease in maternal vitamin D level in neonates with cyanotic CHD (P = 0.000) compared to those with a cyanotic CHD while there was no significant difference in VDR Fok1 genotype (P = 0.18) & allele (P = 0.05) distribution between two groups. We concluded that maternal vitamin D deficiency and VDR gene Fok1 F/f, f/f genotype and f allele were associated with increased risk of CHD in offspring.

Keywords

Vitamin DCongenital heart diseaseFoK1 polymorphismVitamin D receptor geneMaternal vitamin D

References

1

Van der Linde D, Konings EE, Slager MA, et al. Birth prevalence of congenital heart disease worldwide: a systematic review and meta-analysis. J Am Coll Cardiol. 2011;58:2241-2247.
Crossref Google Scholar
2

Botto LD, Correa A. Decreasing the burden of congenital heart anomalies: an epidemiologic evaluation of risk factors and survival. Prog Pediatr Cardiol. 2003;18:111-121.
Crossref Google Scholar
3

Steegers-Theunissen RP, Steegers EA. Nutrient-gene interactions in early pregnancy: a vascular hypothesis. Eur J Obstet Gynecol Reprod Biol. 2003;106:115-117.
Crossref Google Scholar
4

Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357:266-281.
Crossref Google Scholar
5

Hewison M. Vitamin D and the immune system: new perspectives on an old theme. Endocrinol Metab Clin North Am. 2010;39:365-379.
Crossref Google Scholar
6

Bikle DD. Vitamin D: an ancient hormone. Exp Dermatol. 2011;20:7-13.
Crossref Google Scholar
7

Bouillon R, Carmeliet G, Verlinden L, et al. Vitamin D and human health: lessons from vitamin D receptor null mice. Endocr Rev. 2008;29:726-776.
Crossref Google Scholar
8

Taymans SE, Pack S, Pak E, et al. The human vitamin D receptor gene (VDR) is localized to region 12cen-q12 by fluorescent in situ hybridization and radiation hybrid mapping: genetic and physical VDR map. J Bone Mineral Res. 1999;14(7):1163-1166.
Crossref Google Scholar
9

Bobbi L, Lynnette F. Genetic variations in Vitamin D metabolism genes and the microbiome, in the presence of adverse environmental changes, increase immune dysregulation. Austin J Nutr Metab. 2015;2(4):1026.
Google Scholar
10

Zeljic K, Kandolf-Sekulovic L, Supic G, et al. Melanoma risk is associated with vitamin D receptor gene polymorphisms. Melanoma Res. 2014;24:273-279.
Crossref Google Scholar
11

Zeljic K, Supic G, Stamenkovic Radak M, Jovic N, Kozomara R, Magic Z. Vitamin D receptor, cyp27b1 and cyp24a1 genes polymorphisms association with oral cancer risk and survival. J Oral Pathol Med. 2012;41:779-787.
Crossref Google Scholar
12

Joshi L, Ponnana M, Penmetsa SR, Nallari P, Valluri V, Gaddam S. Serum vitamin D levels and VDR polymorphisms (Bsm1 and Fok1) in patients and their household contacts susceptible to tuberculosis. Scand J Immunol. 2014;79:113-119.
Crossref Google Scholar
13

Carvalho C, Marinho A, Leal B, et al. Association between vitamin D receptor (vdr) gene polymorphisms and systemic lupus erythematosus in Portuguese patients. Lupus. 2015;24:846-853.
Crossref Google Scholar
14

Wang TJ, Pencina MJ, Booth SL, et al. Vitamin D deficiency and risk of cardiovascular disease. Circulation. 2008;117:503-511.
Crossref Google Scholar
15

Norman PE, Powell JT. Vitamin D and cardiovascular disease. Circ Res. 2014;114:379-393.
Crossref Google Scholar
16

Kwon HJ. Vitamin D receptor signaling is required for heart development in zebrafish embryo. Biochem Biophys Res Commun. 2016;470:575-578.
Crossref Google Scholar
17

Kim IM, Norris KC, Artaza JN. Vitamin D and cardiac differentiation. Vitam Horm. 2016;100:299-320.
Crossref Google Scholar
18

Botto LD, Mulinare J, Erickson JD. Occurrence of congenital heart defects in relation to maternal multivitamin use. Am J Epidemiol. 2000;51:878-884.
Crossref Google Scholar
19

Holick MF, Binkley NC, Bischoff-Ferrari HA, et al, Endocrine Society. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96:1911-1930.
Crossref Google Scholar
20

McNally JD, Menon K, Lawson ML, Williams KA, Doherty DR. 1, 25 dihydroxyvitamin D deficiency in critically ill children: risk factors and association with clinical course. J Endocrinol Metab. 2015;100:2942-2945.
Crossref Google Scholar
21
International Osteroporosis Foundation. Vitamin D status around the World. Available online: https://www.iofbonehealth.org/facts-and-statistics/vitamin-d-studies-map. Accessed 20 April 2018.
22

Harris SS, Eccleshall TR, Gross C, Dawson-Hughes B, Feldman D. The vitamin D receptor start codon polymorphism (Fok1) and bone mineral density in premenopausal American Black and White women. J Bone Miner Res. 1997;12:1043-1048.
Crossref Google Scholar
23

Holick MF, Chen TC. Vitamin D deficiency: a worldwide problem with health consequences. Am J Clin Nutr. 2008;87:1080S-1086S.
Crossref Google Scholar
24

Halicioglu O, Aksit S, Koc F, et al. Vitamin D deficiency in pregnant women and their neonates in spring time in Western Turkey. Paediatr Perinat Epidemiol. 2012;26:53-60.
Crossref Google Scholar
25

McDonnell SL, Baggerly KA, Baggerly CA, et al. Maternal 25(OH)D concentrations ≥40 ng/mL associated with 60% lower preterm birth risk among general obstetrical patients at an urban medical center. PLoS One. 2017;12(7):e0180483.
Crossref Google Scholar
26

Brade T, Pane LS, Moretti A, Chien KR, Laugwitz KL. Embryonic heart progenitors and cardiogenesis. Cold Spring Harb Perspect Med. 2013;3:a013847.
Crossref Google Scholar
27

Mangelsdorf DJ, Evans RM. The RXR heterodimers and orphan receptors. Cell. 1995;83:841-850.
Crossref Google Scholar
28

Kaludjerovic J, Vieth R. Relationship between vitamin D during perinatal development and health. J Midwifery Womens Health. 2010;55:550-560.
Crossref Google Scholar
29

Bassil D, Rahme M, Hoteit M, Fuleihan G-H. Hypovitaminosis D in the Middle East and North Africa: prevalence, risk factors and impact on outcomes. Derm Endocrinol. 2013;5:274-298.
Crossref Google Scholar
30

El Rifai NM, Abdel Moety GA, Gaafar HM, Hamed DA. Vitamin D deficiency in Egyptian mothers and their neonates and possible related factors. J Matern Fetal Neonatal Med. 2014;27:1064-1068.
Crossref Google Scholar
31

Botros RM, Sabry IM, Abdelbaky RS, Eid YM, Nasr MS, Hendawy LM. Vitamin D deficiency among healthy Egyptian females. Endocrinol Nutr. 2015;62(7):314-321.
Crossref Google Scholar
32

Dilli D, Doğan N, Örün UA, et al. Maternal and neonatal micronutrient levels in newborns with CHD. Cardiol Young. 2018;28:523-529.
Crossref Google Scholar
33

Koster MPH, Van Duijna L, Krul-Poel YHM, et al. A compromised maternal vitamin D status is associated with congenital heart defects in offspring. Early Hum Dev. 2018;117:50-56.
Crossref Google Scholar
34

Whitfield GK, Remus LS, Jurutka PW, Zitzer H, Oza AK, Dang HT. Functionally relevant polymorphisms in the human nuclear vitamin D receptor gene. Mol Cell Endocrinol. 2001;177:145-159.
Crossref Google Scholar
35

Rauch F, Radermacher A, Danz A, et al. Vitamin D receptor genotypes and changes of bone density in physically active German women with high calcium intake. Exp Clin Endocrinol Diabetes. 1997;105:103-108.
Crossref Google Scholar
36

Colin EM, Weel AE, Uitterlinden AG, et al. Consequences of vitamin D receptor gene polymorphisms for growth inhibition of cultured human peripheral blood mononuclear cells by 1, 25-dihydroxyvitamin D3. Clin Endocrinol (Oxf). 2000;52(2):211-216.
Crossref Google Scholar
37

Uitterlinden AG, Pols HA, Burger H, et al. A large-scale population-based study of the association of vitamin D receptor gene polymorphisms with bone mineral density. J Bone Miner Res. 1996;11(9):1241-1248.
Crossref Google Scholar
38

Elsoud MRA, Siyam AHA, Demian SR, Mersal BH. Study of relationship between vitamin D receptor gene polymorphism expression (BSM- I & FOK- I), serum levels of vitamin D and the risk of breast cancer in Egyptian females; correlation with clinicopathological features of the disease. Centre for Info Bio Technol. 2016;6(2):89-99.
Google Scholar
39

Zaki M, Kamal S, Basha WA, et al. Association of vitamin D receptor gene polymorphism (VDR) with vitamin D deficiency, metabolic and inflammatory markers in Egyptian obese women. Genes Dis. 2017;4:176-182.
Crossref Google Scholar
40

Hamed EO, Abdel-Aal AM, Norel Din AK, Atia MMA. Vitamin D level and Fok-I vitamin D receptor gene polymorphism in Egyptian patients with Type-1 diabetes. Egypt J Immunol. 2013;20(2):1-10.
Google Scholar
41

Patel HV, Patel NH, Sodagar NR. Vitamin D receptor (VDR) gene polymorphism and maternal vitamin D deficiency in Indian women with preterm birth (PTB). Asian J Pharm Clin Res. 2017;20(9):219-223.
Crossref Google Scholar
42

Javorski N, Lima CAD, Silva LVC, Crovella S, de Azêvedo Silva J. Vitamin D receptor (VDR) polymorphisms are associated to spontaneous preterm birth and maternal aspects. Gene. 2018;642:58-63.
Crossref Google Scholar
43

Altun Koroglu O, Onay H, Cakmak B, et al. Association of vitamin D receptor polymorphisms and Bronchopulmonary dysplasis. Arch Dis Child. 2012;97:A17-A18.
Crossref Google Scholar
44

Tayel SI, Soliman SE, Elsayed HM. Vitamin D deficiency and vitamin D receptor variants in mothers and their neonates are risk factors for neonatal sepsis. Steroids. 2018;134:37-42.
Crossref Google Scholar
45

Bhanushali AA, Lajpal N, Kulkarni SS, Chavan SS, Bagadi SS, Das BR. Frequency of fokI and taqI polymorphism of vitamin D receptor gene in Indian population and its association with 25-hydroxyvitamin D levels. Indian J Hum Genet. 2009;15(3):108-113.
Crossref Google Scholar
Genes & Diseases
Volume 6 Issue 2,
June 2019
Pages 193-200
DOI: 10.1016/j.gendis.2018.08.001
Cite this article:
Mokhtar WA, Fawzy A, Allam RM, et al. Maternal vitamin D level and vitamin D receptor gene polymorphism as a risk factor for congenital heart diseases in offspring; An Egyptian case-control study. Genes & Diseases, 2019, 6(2): 193-200. https://doi.org/10.1016/j.gendis.2018.08.001

243

Views

2

Downloads

12

Crossref

N/A

Web of Science

10

Scopus

0

CSCD

Altmetrics
Received: 07 July 2018
Accepted: 15 August 2018
Published: 26 August 2018
© 2018, Chongqing Medical University.

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Return