Increased vitamin D receptor gene expression and rs11568820 and rs4516035 promoter polymorphisms in autistic disorder

Abstract

Although there are a large number of sequence variants of different genes and copy number variations at various loci identified in autistic disorder (AD) patients, the pathogenesis of AD has not been elucidated completely. Recently, in AD patients, a large number of expression array and transcriptome studies have shown an increase in the expression of genes especially related to innate immune response. Antimicrobial effects of vitamin D and VDR are exerted through Toll-Like-Receptors (TLR) which have an important role in the innate immune response, are expressed by antigen presenting cells and recognize foreign microorganisms. In this study, age and gender matched 30 patients diagnosed with AD and 30 healthy controls were included in the study. Comparatively whole blood VDR gene expression and rs11568820 and rs4516035 SNP profile of the promoter region of the VDR gene were investigated by real time PCR. Whole blood VDR gene expression was significantly higher in the AD group compared to control subjects (p < 0.0001). There were no significant differences among allele and genotype distribution of rs11568820 and rs4516035 polymorphisms between AD patients and controls. The increase of VDR gene expression in patients with AD may be in accordance with an increase in the innate immune response in patients with AD. Furthermore, this study will stimulate new studies in order to clarify the relationship among AD, vitamin D, VDR, and innate immunity.

Fok-I, Bsm-I, and Taq-I Variants of Vitamin D Receptor Polymorphism in the Development of Autism Spectrum Disorder: A Literature Review

“…Allele t and A were found to be predominant in ASD patients [ 36 - 38 ]. An association between female gender and allele T was found supporting the study that autism is more common in a male gender as T allele is less frequently present in a male child [ 36 , 40 - 41 ]. There were few studies which founded an association between VDR gene polymorphisms and serum 25(OH)D level.…”

“…The anti-inflammatory action of vitamin D has an active role in regulating the immune function of the human body. The increased risk of getting tuberculosis infection in patients with 1,25(OH)2D3 deficiency supports the role of VDR and 1,25(OH)2D3 in innate immunity [ 40 , 49 ].…”

“…Restriction fragment length polymorphism (RFLP) assay done using different enzymes showed important polymorphisms in the VDR gene. In intron 8, there was detection of polymorphisms by the restriction enzyme Apa-I A/a(adenine>cytosine)(rs797532) and BsmIB/b(adenine>guanine) (rs1544410) [ 37 , 40 ]. Several other polymorphisms also got detected which also affect gene expressions such as rs 731236(Taq 1) at exon 9 and rs11568829 Caudal type Homeobox 2(Cdx2) in the promoter region.…”

“…The rs 2228570(Fok1) is in exon two which can alter the transcription initiation site due to polymorphism which eventually produces two different sized proteins. The VDR polymorphism can play a role in the development of ASD by influencing the action pathway of vitamin D [ 36 - 40 ].…”

“…Paternal homozygous VDR TaqI and BsmI variants showed some relation with ASD [ 40 , 43 ]. The male reproductive tract has VDR and vitamin D metabolizing enzymes [ 44 - 45 ].…”