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Archives of Gynecology and Obstetrics

Published in:

01-08-2017 | Maternal-Fetal Medicine

Maternal–fetal vitamin D receptor polymorphisms significantly associated with preterm birth

Authors: Talya Rosenfeld, Hagit Salem, Gheona Altarescu, Sorina Grisaru-Granovsky, Aharon Tevet, Ruth Birk

Published in: Archives of Gynecology and Obstetrics | Issue 2/2017

Abstract

Purpose

Preterm birth (PTB) is a complex trait with strong genetic background, whose etiology is not fully understood. It was recently suggested that pregnancy duration is affected by fetal genetic variation even more than by the maternal genome. Vitamin D receptor (VDR) is involved in embryonic implantation and fertility. We studied the association between both maternal and neonatal vitamin D receptor (VDR) genetic variation and PTB.

Methods

Maternal and fetal (umbilical cord) DNA was isolated from Jewish Israeli idiopathic preterm newborns (24–36 weeks, n = 146) and control term newborns (>37 weeks, n = 229). Maternal and fetal VDR polymorphisms (FokI, ApaI, BsmI, TaqI) were analyzed by restriction fragment length polymorphism analysis. Using SPSS analysis to correlate VDR genotypes with phenotypic variation: pregnancy duration, preterm birth and spontaneous miscarriages, adjusted for gravidity, parity and gender of newborn.

Results

Women homozygous to VDR ApaI (AA) genotype had significant twofold increase risk for PTB [OR 1.973, (CI) 1.183–3.289, p = 0.009] compared to heterozygous women. Male newborns had significant (p < 0.05) 1.73-fold increase of PTB. Women with history of previous (≥1) spontaneous miscarriage had a significant increased risk for PTB if their newborn carried either of the VDR BsmI homozygous (BB or bb) genotypes compared to the heterozygous (Bb) genotype [OR 6.857, (CI) 1.273–36.934, p = 0.018 and OR 9.231, (CI) 1.753–48.618, p = 0.008, respectively], or VDR ApaI homozygous (AA or aa) genotype compared to heterozygous (Aa) genotype [OR 4.33, (CI) 1.029–18.257, p = 0.046 and OR 7.2, (CI) 1.34–38.917, p = 0.021, respectively].

Conclusions

We show association between maternal and fetal VDR genotype variants with PTB.

Goldenberg RL, Culhane JF, Iams JD, Romero R (2008) Epidemiology and causes of preterm birth. Lancet Lond Engl 371:75–84. doi:10.1016/S0140-6736(08)60074-4 CrossRef

York TP, Eaves LJ, Neale MC, Strauss JF (2014) The contribution of genetic and environmental factors to the duration of pregnancy. Am J Obstet Gynecol 210:398–405. doi:10.1016/j.ajog.2013.10.001 CrossRefPubMed

Crider KS, Whitehead N, Buus RM (2005) Genetic variation associated with preterm birth: review. Genet Med Off J Am Coll Med Genet 7:593–604. doi:10.109701.gim.0000187223.69947.db

Grisaru-Granovsky S, Tevet A, Bar-Shavit R, Salah Z, Elstein D, Samueloff A, Altarescu G (2007) Association study of protease activated receptor 1 gene polymorphisms and adverse pregnancy outcomes: results of a pilot study in Israel. Am J Med Genet A 143A:2557–2563. doi:10.1002/ajmg.a.31985 CrossRefPubMed

Siddesh A, Parveen F, Misra MK, Phadke SR, Agrawal S (2014) Platelet-specific collagen receptor glycoprotein VI gene variants affect recurrent pregnancy loss. Fertil Steril 102(1078–1084):e3. doi:10.1016/j.fertnstert.2014.07.002

Rai V (2014) Methylenetetrahydrofolate reductase gene A1298C polymorphism and susceptibility to recurrent pregnancy loss: a meta-analysis. Cell Mol Biol Noisy Gd Fr 60:27–34 (PMID: 24970119)

Alkhuriji AF, Alhimaidi AR, Babay ZA, Wary AS (2013) The relationship between cytokine gene polymorphism and unexplained recurrent spontaneous abortion in Saudi females. Saudi Med J 34:484–489 (PMID: 23677264)PubMed

Christakos S, DeLuca HF (2011) Minireview: vitamin D: is there a role in extraskeletal health? Endocrinology 152:2930–2936. doi:10.1210/en.2011-0243 CrossRefPubMedPubMedCentral

Mahon P, Harvey N, Crozier S, Inskip H, Robinson S, Arden N, Swaminathan R, Cooper C, Godfrey K (2010) SWS Study Group Low maternal vitamin D status and fetal bone development: cohort study. J Bone Miner Res Off J Am Soc Bone Miner Res 25:14–19. doi:10.1359/jbmr.090701 CrossRef

10.

Liu NQ, Hewison M (2012) Vitamin D, the placenta and pregnancy. Arch Biochem Biophys 523:37–47. doi:10.1359/jbmr.090701 CrossRefPubMed

11.

Aghajafari F, Nagulesapillai T, Ronksley PE, Tough SC, O’Beirne M, Rabi DM (2013) Association between maternal serum 25-hydroxyvitamin D level and pregnancy and neonatal outcomes: systematic review and meta-analysis of observational studies. BMJ 346:f1169 (PMID: 23533188) CrossRefPubMed

12.

Barrera D, Avila E, Hernández G, Méndez I, González L, Halhali A, Larrea F, Morales A, Díaz L (2008) Calcitriol affects hCG gene transcription in cultured human syncytiotrophoblasts. Reprod Biol Endocrinol 6:3. doi:10.1186/1477-7827-6-3 CrossRefPubMedPubMedCentral

13.

Salamonsen LA, Nie G, Findlay JK (2002) Newly identified endometrial genes of importance for implantation. J Reprod Immunol 53:215–225 (PMID: 11730918)CrossRefPubMed

14.

Evans KN, Bulmer JN, Kilby MD, Hewison M (2004) Vitamin D and placental-decidual function. J Soc Gynecol Investig 11:263–271. doi:10.1016/j.jsgi.2004.02.002 CrossRefPubMed

15.

Viganò P, Mangioni S, Pompei F, Chiodo I (2003) Maternal-conceptus cross talk—a review. Placenta 24(Suppl B):S56–S61 (PMID: 14559031)

16.

Piccinni MP, Scaletti C, Maggi E, Romagnani S (2000) Role of hormone-controlled Th1- and Th2-type cytokines in successful pregnancy. J Neuroimmunol 109:30–33 (PMID: 10969178)CrossRefPubMed

17.

Qin L-L, Lu F-G, Yang S-H, Xu H-L, Luo B-A (2016) Does maternal vitamin D deficiency increase the risk of preterm birth: a meta-analysis of observational studies. Nutrients 20:8. doi:10.3390/nu8050301

18.

Fischer-Suárez N, Fernández-Alonso AM, Herrera-Muñoz A, Chedraui P, Pérez-López FR (2016) Maternal serum 25-hydroxyvitamin D and C-reactive protein levels in pregnancies complicated with threatened preterm labour. Gynecol Endocrinol 32:777–781. doi:10.1080/09513590.2016.1177011 CrossRefPubMed

19.

Santoro D, Gagliostro G, Alibrandi A, Ientile R, Bellinghieri G, Savica V, Buemi M, Caccamo D (2014) Vitamin D receptor gene polymorphism and left ventricular hypertrophy in chronic kidney disease. Nutrients 6:1029–1037. doi:10.3390/nu6031029 CrossRefPubMedPubMedCentral

20.

Kanan RM (2013) The effect of FokI vitamin D receptor polymorphism on bone mineral density in Jordanian perimenopausal women. Indian J Hum Genet 19:233–238. doi:10.4103/0971-6866.116125 CrossRefPubMedPubMedCentral

21.

Rojano-Mejía D, Coral-Vázquez RM, Coronel A, Cortes-Espinosa L, del Carmen Aguirre-García M, Valencia-Villalvazo EY, Canto P (2014) Relation of the estrogen receptor and vitamin D receptor polymorphisms with bone mineral density in postmenopausal Mexican-mestizo women. Gene 537:10–14. doi:10.1016/j.gene.2013.12.054 CrossRefPubMed

22.

Shan J, Dai N, Yang XQ, Qian CY, Yang ZZ, Jin F, Li M, Wang D (2014) FokI polymorphism in vitamin D receptor gene and risk of breast cancer among Caucasian women. Tumour Biol 35:3503–3508. doi:10.1007/s13277-013-1462-z CrossRefPubMed

23.

Zhu B, Zhao HL, Ou C, Huang LS, Li PZ, Lao M (2014) Association of vitamin D receptor BsmI gene polymorphism with the risk of type 2 diabetes mellitus. J Recept Signal Transduct Res 34:458–462. doi:10.3109/10799893.2014.919592 CrossRefPubMed

24.

Vasilopoulos Y, Sarafidou T, Kotsa K, Papadimitriou M, Goutzelas Y, Stamatis C, Bagiatis V, Tsekmekidou X, Yovos JG, Mamuris Z (2013) VDR TaqI is associated with obesity in the Greek population. Gene 512:237–239. doi:10.1016/j.gene.2012.10.044 CrossRefPubMed

25.

Aslani S, Hossein-Nezhad A, Mirzaei K, Maghbooli Z, Afshar AN, Karimi F (2011) VDR FokI polymorphism and its potential role in the pathogenesis of gestational diabetes mellitus and its complications. Gynecol Endocrinol 27:1055–1060. doi:10.3109/09513590.2011.569786 CrossRefPubMed

26.

Fang X, Li H, Diao Y, Shan R, Dong J, Li H, Ma Q, Hou Y, Kong B (2010) Cui J (2010) Polymorphisms in the MTHRF, VDR, MMP-9 and IL-β genes and the risk of premature rupture of membranes. Gynecol Obstet Invest 70:206–214. doi:10.1159/000318867 CrossRefPubMed

27.

Valdivielso JM, Fernandez E (2006) Vitamin D receptor polymorphisms and diseases. Clin Chim Acta Int J Clin Chem 371:1–12. doi:10.1016/j.cca.2006.02.016 CrossRef

28.

Bodnar LM, Catov JM, Zmuda JM, Cooper ME, Parrott MS, Roberts JM, Marazita ML, Simhan HN (2010) Maternal serum 25-hydroxyvitamin D concentrations are associated with small-for-gestational age births in white women. J Nutr 140:999–1006. doi:10.3945/jn.109.119636 CrossRefPubMedPubMedCentral

29.

Uitterlinden AG, Fang Y, Van Meurs JBJ, Pols HAP, Van Leeuwen JPTM (2004) Genetics and biology of vitamin D receptor polymorphisms. Gene 338:143–156. doi:10.1016/j.gene.2004.05.014 CrossRefPubMed

30.

Nasiri H, Forouzandeh M, Rasaee MJ, Rahbarizadeh F (2005) Modified salting-out method: high-yield, high-quality genomic DNA extraction from whole blood using laundry detergent. J Clin Lab Anal 19:229–232. doi:10.1016/j.gene.2004.05.014 CrossRefPubMed

31.

Mizutani S, Wright J, Kobayashi H (2011) A new approach regarding the treatment of preeclampsia and preterm labor. Life Sci 88:17–23. doi:10.1016/j.lfs.2010.10.013 CrossRefPubMed

32.

Swingle HM, Colaizy TT, Zimmerman MB, Morriss FH (2009) Abortion and the risk of subsequent preterm birth: a systematic review with meta-analyses. J Reprod Med 54:95–108 (PMID: 19301572)PubMed

33.

McElrath TF, Hecht JL, Dammann O, Boggess K, Onderdonk A, Markenson G, Harper M, Delpapa E, Allred EN, Leviton A (2008) Pregnancy disorders that lead to delivery before the 28th week of gestation: an epidemiologic approach to classification. Am J Epidemiol 168:980–989. doi:10.1093/aje/kwn202 CrossRefPubMedPubMedCentral

34.

Carless MA, Kraska T, Lintell N, Neale RE, Green AC, Griffiths LR (2008) Polymorphisms of the VDR gene are associated with presence of solar keratoses on the skin. Br J Dermatol 159:804–810. doi:10.1111/j.1365-2133.2008.08745.x CrossRefPubMed

35.

Joos L, Weir TD, Connett JE, Anthonisen NR, Woods R, Paré PD, Sandford AJ (2003) Polymorphisms in the beta2 adrenergic receptor and bronchodilator response, bronchial hyperresponsiveness, and rate of decline in lung function in smokers. Thorax 58:703–707 (PMCID: PMC1746784)

36.

Taboulet J, Frenkian M, Frendo JL, Feingold N, Jullienne A, de Vernejoul MC (1998) Calcitonin receptor polymorphism is associated with a decreased fracture risk in post-menopausal women. Hum Mol Genet 7:2129–2133 (PMID: 9817931)CrossRefPubMed

37.

Arking DE, Atzmon G, Arking A, Barzilai N, Dietz HC (2005) Association between a functional variant of the KLOTHO gene and high-density lipoprotein cholesterol, blood pressure, stroke, and longevity. Circ Res 96:412–418. doi:10.1161/01.RES.0000157171.04054.30 CrossRefPubMed

38.

Morrison NA, Qi JC, Tokita A, Kelly PJ, Crofts L, Nguyen TV, Sambrook PN, Eisman JA (1994) Prediction of bone density from vitamin D receptor alleles. Nature 367:284–287. doi:10.1038/367284a0 CrossRefPubMed

39.

Marco MP, Martínez I, Amoedo ML, Borràs M, Saracho R, Almirall J, Fibla J, Fernández E (1999) Vitamin D receptor genotype influences parathyroid hormone and calcitriol levels in predialysis patients. Kidney Int 56:1349–1353. doi:10.1038/367284a0 CrossRefPubMed

40.

Takeyama K, Kitanaka S, Sato T, Kobori M, Yanagisawa J, Kato S (1997) 25-Hydroxyvitamin D3 1alpha-hydroxylase and vitamin D synthesis. Science 277:1827–1830 (PMID: 9295274)CrossRefPubMed

41.

Rezende VB, Sandrim VC, Palei AC, Machado L, Cavalli RC, Duarte G, Tanus-Santos JE (2012) Vitamin D receptor polymorphisms in hypertensive disorders of pregnancy. Mol Biol Rep 39:10903–10906. doi:10.1007/s11033-012-1988-y CrossRefPubMed

42.

Morley R, Carlin JB, Pasco JA, Wark JD, Ponsonby A-L (2009) Maternal 25-hydroxyvitamin D concentration and offspring birth size: effect modification by infant VDR genotype. Eur J Clin Nutr 63:802–804. doi:10.1038/ejcn.2008.55 CrossRefPubMed

43.

Thota C, Menon R, Fortunato SJ, Brou L, Lee JE, Al-Hendy A (2014) 1,25-Dihydroxyvitamin D deficiency is associated with preterm birth in African American and Caucasian women. Reprod. Sci. Thousand Oaks Calif 21:244–250. doi:10.1177/1933719113493513 CrossRef

44.

Weinert LS, Silveiro SP (2015) Maternal–fetal impact of vitamin D deficiency: a critical review. Matern Child Health J 19:94–101. doi:10.1007/s10995-014-1499-7 CrossRefPubMed

45.

Bodnar LM, Catov JM, Simhan HN, Holick MF, Powers RW, Roberts JM (2007) Maternal vitamin D deficiency increases the risk of preeclampsia. J Clin Endocrinol Metab 92:3517–3522. doi:10.1210/jc.2007-0718 CrossRefPubMedPubMedCentral

46.

August P, Marcaccio B, Gertner JM, Druzin ML, Resnick LM, Laragh JH (1992) Abnormal 1,25-dihydroxyvitamin D metabolism in preeclampsia. Am J Obstet Gynecol 166:1295–1299 (PMID: 1566788)CrossRefPubMed

47.

Novakovic B, Sibson M, Ng HK, Manuelpillai U, Rakyan V, Down T, Beck S, Fournier T, Evain-Brion D, Dimitriadis E, Craig JM, Morley R, Saffery R (2009) Placenta-specific methylation of the vitamin D 24-hydroxylase gene: implications for feedback autoregulation of active vitamin D levels at the fetomaternal interface. J Biol Chem 284:14838–14848. doi:10.1074/jbc.M809542200 CrossRefPubMedPubMedCentral

48.

Liu PT, Stenger S, LiH Wenzel L, Tan BH, Krutzik SR, Ochoa MT, Schauber J, Wu K, Meinken C et al (2006) Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science 311:1770–1773. doi:10.1126/science.1123933 CrossRefPubMed

49.

Esplin MS, Manuck TA, Varner MW, Christensen B, Biggio J, Bukowski R, Parry S, Zhang H, Huang H, Andrews W et al (2015) Cluster analysis of spontaneous preterm birth phenotypes identifies potential associations among preterm birth mechanisms. Am J Obstet Gynecol 213:429.e1–429.e9. doi:10.1016/j.ajog.2015.06.011

Title: Maternal–fetal vitamin D receptor polymorphisms significantly associated with preterm birth
Authors: Talya Rosenfeld
Hagit Salem
Gheona Altarescu
Sorina Grisaru-Granovsky
Aharon Tevet
Ruth Birk
Publication date: 01-08-2017
Publisher: Springer Berlin Heidelberg
Published in: Archives of Gynecology and Obstetrics / Issue 2/2017
Print ISSN: 0932-0067
Electronic ISSN: 1432-0711
DOI: https://doi.org/10.1007/s00404-017-4412-y

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Maternal–fetal vitamin D receptor polymorphisms significantly associated with preterm birth

Abstract

Purpose

Methods

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

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