There is a significant association exists between vitamin D deficiencies, low respiratory tract infections, and certain types of VDR gene polymorphism. Various studies are being conducted to prove any such link between the different clinical conditions due to disturbed vitamin D regulation and VDR gene polymorphisms. The present study analyzed the presence of vitamin D receptor (VDR) gene polymorphisms (ApaI and TaqI) in Saudi pediatric patient suffering from acute lower respiratory tract infection (ALRTI) cases. Fifty children (50) with ALRTI admitted at King Saud University Medical City, Riyadh/Saudi Arabia were included in addition to seventy-three (73) apparently healthy children who were considered as the control group. Genomic DNA from whole blood was extracted and subjected to polymerase chain reaction (PCR) targeting TaqI and ApaI VDR polymorphisms. RFLP–PCR genotyping was performed to determine the allelic frequency within the VDR gene. In the whole sample, the allelic frequency of ApaI polymorphism in the VDR gene was 58.5%, 17.9%, and 23.6% for AA, Aa, and aa respectively (p = 0.11), while it was 48%, 19%, and 33% for TT, Tt, and tt respectively (p = 0.33) with regards to the frequency of TaqI polymorphism in the VDR gene. VDR ApaI Aa and aa genotypes and VDR TaqI Tt and tt genotypes were not associated with increased risk of ALRTI in children (OR 0.87, 95% CI 0.33–2.28, p = 0.77; OR 0.56, 95% CI 0.23–1.4, p = 0.21; OR 1.15, 95% CI 0.44–2.99, p = 0.77; OR 0.73, 95% CI 0.32–1.68, p = 0.46 respectively). To conclude, neither vitamin D status nor VDR gene polymorphisms such as ApaI and TaqI is associated with increased susceptibility to ALRTI. Linkage disequilibrium was not detected between ApaI and TaqI VDR gene polymorphisms as in the case of serum vitamin D status in ALRTI patients versus apparent healthy children.
Acute lower respiratory tract infection Gene polymorphism Saudi children Vitamin D receptor
This is a preview of subscription content, log in to check access.
The authors would like to thank the Deanship of Scientific Research, and Research Center, College of pharmacy King Saud University, Riyadh, Saudi Arabia for assisting this study.
Somaya Al Gowhary and Nermin Hassan prepared the plan for the study and supervised the design and execution. Enas Zakaria, Amal Fatani provided the materials and kits required in the lab. Sarah and Manal facilitated the hospital communication and provided clinical data. Enas Zakaria also collected the samples and performed the laboratory work. Wael Mansy wrote the paper, Fadwa Abdel Reheem and Heba Al Awady reviewed it.
Compliance with ethical standards
Conflict of interest
The authors declare no conflicts of interest.
Miyamoto K-i, Kesterson RA, Yamamoto H et al (1997) Structural organization of the human vitamin D receptor chromosomal gene and its promoter. Mol Endocrinol 11(8):1165–1179CrossRefGoogle Scholar
Vanessa O, Asani FF, Jeffery TJ, Saccone DS, Bornman L (2013) Vitamin D receptor gene expression and function in a South African population: ethnicity, vitamin D and FokI. PLoS ONE 8(6):e67663CrossRefGoogle Scholar
Walker VP, Modlin RL (2009) The vitamin D connection to pediatric infections and immune function. Pediatr Res 65(5):106RCrossRefGoogle Scholar
Muhe L, Lulseged S, Mason KE, Simoes EA (1997) Case-control study of the role of nutritional rickets in the risk of developing pneumonia in Ethiopian children. Lancet 349(9068):1801–1804CrossRefGoogle Scholar
Mansy W, Zakaria EA, Somaya E-G, Alsubaie SS, Manal M (2016) Evaluation of serum vitamin D, LL37 and interferon gamma levels in Saudi children with acute lower respiratory tract infection. Int J Pharm Res Allied Sci 5:180–190Google Scholar
Karatekin G, Kaya A, Salihoğlu Ö, Balci H, Nuhoğlu A (2009) Association of subclinical vitamin D deficiency in newborns with an acute lower respiratory infection and their mothers. Eur J Clin Nutr 63(4):473CrossRefGoogle Scholar
Uitterlinden AG, Fang Y, van Meurs JB, Pols HA (2005) Genetic vitamin D receptor polymorphisms and risk of disease. Vitamin D 2:1121–1157CrossRefGoogle Scholar
Risch N, Merikangas K (1996) The future of genetic studies of complex human diseases. Science 273(5281):1516–1517CrossRefGoogle Scholar
Faraco JH, Morrison NA, Baker A, Shine J, Frossard PM (1989) ApaI dimorphism at the human vitamin D receptor gene locus. Nucl Acids Res 17:2450CrossRefGoogle Scholar
Jurutka PW, Remus LS, Whitfield GK, Thompson PD, Hsieh JC et al (2000) The polymorphic N terminus in human vitamin D receptor isoforms influences transcriptional activity by modulating interaction with transcription factor IIB. Mol Endocrinol 14:401–420CrossRefGoogle Scholar
Fang Y, Rivadeneira F, van Meurs JB, Pols HA, Ioannidis JP, Uitterlinden AG (2006) Vitamin D receptor gene BsmI and TaqI polymorphisms and fracture risk: a meta-analysis. Bone 39(4):938–945CrossRefGoogle Scholar
Valdivielso JM, Fernandez E (2006) Vitamin D receptor polymorphisms and diseases. Clin Chim Acta 371(1–2):1–12CrossRefGoogle Scholar
Roth DE, Jones AB, Prosser C, Robinson JL, Vohra S (2008) Vitamin D receptor polymorphisms and the risk of acute lower respiratory tract infection in early childhood. J Infect Dis 197(5):676–680CrossRefGoogle Scholar
Dusso AS, Brown AJ, Slatopolsky E. Vitamin D (2005) Vitamin D. Am J Physiol Renal Physiol 289(1):F8–F28CrossRefGoogle Scholar
McNally JD, Leis K, Matheson LA, Karuananyake C, Sankaran K, Rosenberg AM (2009) Vitamin D deficiency in young children with severe acute lower respiratory infection. Pediatr Pulmonol 44(10):981–988CrossRefGoogle Scholar
Riggs LB, Nguyen TV, Melton JL III et al (1995) The contribution of vitamin D receptor gene alleles to the determination of bone mineral density in normal and osteoporotic women. J Bone Miner Res 10(6):991–996CrossRefGoogle Scholar
Karasneh JA, Ababneh KT, Taha AH et al (2013) Association of vitamin D receptor gene polymorphisms with chronic and aggressive periodontitis in Jordanian patients. Eur J Oral Sci 121(6):551–558CrossRefGoogle Scholar
Ogunkolade B-W, Boucher BJ, Prahl JM et al (2002) Vitamin D receptor (VDR) mRNA and VDR protein levels in relation to vitamin D status, insulin secretory capacity, and VDR genotype in Bangladeshi Asians. Diabetes 51(7):2294–2300CrossRefGoogle Scholar
Drysdale SB, Alcazar M, Wilson T et al (2016) Functional and genetic predisposition to rhinovirus lower respiratory tract infections in prematurely born infants. Eur J Pediatr 175(12):1943–1949CrossRefGoogle Scholar
Nosratabadi R, Arababadi M, Salehabad V et al (2010) Polymorphisms within exon 9 but not intron 8 of the vitamin D receptor are associated with the nephropathic complication of type-2 diabetes. Int J Immunogenet 37(6):493–497CrossRefGoogle Scholar
Kang TJ, Jin SH, Yeum C-E et al (2011) Vitamin D receptor gene TaqI, BsmI and FokI polymorphisms in Korean patients with tuberculosis. Immune Netw 11(5):253–257CrossRefGoogle Scholar
Ewald B, Eun-Kyun S, Richard MW, Thomas L, Dieter SW, Simon P (1996) Genotypes of the vitamin-D-receptor gene and bone mineral density in Caucasoid postmenopausal females. Maturitas 24(1):91–96CrossRefGoogle Scholar
Zmuda JM, Cauley JA, Danielson ME, Wolf RL, Ferrell RE (1997) Vitamin D receptor gene polymorphisms, bone turnover, and rates of bone loss in older African-American women. J Bone Miner Res 12(9):1446–1452CrossRefGoogle Scholar
Bid HK, Mishra DK, Mittal RD (2005) Vitamin-D receptor (VDR) gene (Fok-I, Taq-I and Apa-I) polymorphisms in healthy individuals from north Indian Population. Asian Pac J Cancer Prev 6:147–152Google Scholar
Sainz J, Van Tornout JM, Loro ML, Sayre J, Roe TF, Gilsanz V (1997) Vitamin D–receptor gene polymorphisms and bone density in prepubertal American girls of Mexican descent. N Engl J Med 337(2):77–82CrossRefGoogle Scholar
Das B, Patra S, Behera C, Suar M (2016) Genotyping of vitamin D receptor gene polymorphisms using mismatched amplification mutation assay in neonatal sepsis patients of Odisha, eastern India. Infect Genet Evolut 45:40–47CrossRefGoogle Scholar
Wilkinson RJ, Llewelyn M, Toossi Z et al (2000) Influence of vitamin D deficiency and vitamin D receptor polymorphisms on tuberculosis among Gujarati Asians in west London: a case-control study. Lancet 355(9204):618–621CrossRefGoogle Scholar
Martineau AR, Timms PM, Bothamley GH, Hanifa Y, Islam K et al (2011) High-dose vitamin D(3) during intensive-phase antimicrobial treatment of pulmonary tuberculosis: a double-blind randomized controlled trial. Lancet 377:242–250CrossRefGoogle Scholar
Haddad S (2014) Vitamin-D receptor (VDR) gene polymorphisms (Taq-I & Apa-I) in Syrian healthy population. Meta Gene 2:646–650CrossRefGoogle Scholar
Kung A, Yeung S, Lau K (1998) Vitamin D receptor gene polymorphisms and peak bone mass in southern Chinese women. Bone 22(4):389–393CrossRefGoogle Scholar
Ongphiphadhanakul B, Rajatanavin R, Chanprasertyothin S et al (1997) Vitamin D receptor gene polymorphism is associated with urinary calcium excretion but not with bone mineral density in postmenopausal women. J Endocrinol Investig 20(10):592–596CrossRefGoogle Scholar
Tokitan A, Matsumoto H, Morrison NA et al (1996) Vitamin D receptor alleles, bone mineral density and turnover in premenopausal Japanese women. J Bone Miner Res 11(7):1003–1009CrossRefGoogle Scholar