Genetic polymorphisms in folate pathway enzymes, DRD4 and GSTM1 are related to temporomandibular disorder

Abstract

BackgroundTemporomandibular disorder (TMD) is a multifactorial syndrome related to a critical period of human life. TMD has been associated with psychological dysfunctions, oxidative state and sexual dimorphism with coincidental occurrence along the pubertal development. In this work we study the association between TMD and genetic polymorphisms of folate metabolism, neurotransmission, oxidative and hormonal metabolism. Folate metabolism, which depends on genes variations and diet, is directly involved in genetic and epigenetic variations that can influence the changes of last growing period of development in human and the appearance of the TMD.MethodsA case-control study was designed to evaluate the impact of genetic polymorphisms above described on TMD. A total of 229 individuals (69% women) were included at the study; 86 were patients with TMD and 143 were healthy control subjects. Subjects underwent to a clinical examination following the guidelines by the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD). Genotyping of 20 Single Nucleotide Polymorphisms (SNPs), divided in two groups, was performed by multiplex minisequencing preceded by multiplex PCR. Other seven genetic polymorphisms different from SNPs (deletions, insertions, tandem repeat, null genotype) were achieved by a multiplex-PCR. A chi-square test was performed to determine the differences in genotype and allelic frequencies between TMD patients and healthy subjects. To estimate TMD risk, in those polymorphisms that shown significant differences, odds ratio (OR) with a 95% of confidence interval were calculated.ResultsSix of the polymorphisms showed statistical associations with TMD. Four of them are related to enzymes of folates metabolism: Allele G of Serine Hydoxymethyltransferase 1 (SHMT1) rs1979277 (OR = 3.99; 95%CI 1.72, 9.25; p = 0.002), allele G of SHMT1 rs638416 (OR = 2.80; 95%CI 1.51, 5.21; p = 0.013), allele T of Methylentetrahydrofolate Dehydrogenase (MTHFD) rs2236225 (OR = 3.09; 95%CI 1.27, 7.50; p = 0.016) and allele A of Methionine Synthase Reductase (MTRR) rs1801394 (OR = 2.35; 95CI 1.10, 5.00; p = 0.037). An inflammatory oxidative stress enzyme, Gluthatione S-Tranferase Mu-1(GSTM1), null allele (OR = 2.21; 95%CI 1.24, 4.36; p = 0.030) and a neurotransmission receptor, Dopamine Receptor D4 (DRD4), long allele of 48 bp-repeat (OR = 3.62; 95%CI 0.76, 17.26; p = 0.161).ConclusionsSome genetic polymorphisms related to folates metabolism, inflammatory oxidative stress, and neurotransmission responses to pain, has been significantly associated to TMD syndrome

Effect of Human Genetic Variability on Gene Expression in Dorsal Root Ganglia and Association with Pain Phenotypes

“…However, a fair number of candidate gene-based studies have reported genes associated with various chronic pain conditions, including temporomandibular disorders (TMD) (Aneiros-Guerrero et al, 2011; Smith et al, 2011), fibromyalgia (FM) (Smith et al, 2012), and lower back pain (LBP) (Guo et al, 2011). To assemble a list of SNPs currently associated with human pain conditions, we used the Human Pain Genetics Database (http://diatchenko.lab.mcgill.ca/hpgdb/), a hand-curated literature survey of genetic associations related to human pain phenotypes.…”

Pain Mechanisms and Centralized Pain in Temporomandibular Disorders

“…Another recent study indicated monoamine involvement in TMD, as 1 SNP of the dopamine receptor 4 gene confers additional TMD risk (Aneiros-Guerrero et al 2011).…”

The temporomandibular joint of California sea lions (Zalophus californianus): Part 2-osteoarthritic changes

“…[34][35][36][37][38][39] Given the high occurrence of TMJ-OA in California sea lions, it is possible that genetic factors may play a role in the disease occurrence or the underlying process, as seen in humans with TMJ disorders. [40][41][42] Furthermore, unlike previously described TMJ disorders in other animals, 9,10 the distribution of TMJ-OA in the California sea lion demonstrated that the OA changes at the mandibular fossa are more severe and more localized to the medial aspect. While it is difficult to assert the reasons for this occurrence, it is possible that the TMJ is less stable at the medial aspect and that this may be unique to the nonmasticatory adaptation of the sea lions.…”