Family-based study of association between ENPP1 genetic variants and craniofacial morphology

Ermakov, Sergey; Rosenbaum, Michael G.; Malkin, Ida; Livshits, Gregory

doi:10.3109/03014461003639231

Cited by 12 publications

(11 citation statements)

References 45 publications

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“…47 The SNP has also been associated to changes in bigonial width dimension in Western Eurasians. 48 This corroborates our finding that rs6560759 is significantly different in group 1, which has asymmetry in mandibular body breadth, but not in ramus height. Rs858339 is an intronic SNP previously associated with variation in bone mineral density.…”

Section: Discussionsupporting

confidence: 91%

ENPP1 and ESR1 genotypes associated with subclassifications of craniofacial asymmetry and severity of temporomandibular disorders

Chung

Richards

Nicot

et al. 2017

American Journal of Orthodontics and Dentofacial Orthopedics

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Introduction We investigated if ACTN3, ENPP1, ESR1, PITX1 and PITX2 genes which contribute to sagittal and vertical malocclusion also contribute to facial asymmetries and TMD before and after orthodontic and orthognathic surgery treatment. Methods One hundred seventy four dentofacial deformity patients were diagnosed as symmetric or subdivided into four asymmetric groups according to PA cephalometric measurements. TMD exam diagnosis and Jaw Pain and Function-(JPF) questionnaires assessed presence and severity of TMD. Results Fifty two % of patients were symmetric and forty eight % asymmetric. The asymmetry classification demonstrated significant cephalometric differences between symmetric and asymmetric groups, and across the four asymmetric subtypes: Group 1 - mandibular body asymmetry, Group 2 - ramus asymmetry, Group 3 - atypical asymmetry and Group 4 - “C-shaped” asymmetry. ENPP1 SNP-rs6569759 associated with asymmetry Group 1(p=0.004), and rs858339 with asymmetry Group 3 (p=0.002). ESR1 SNP-rs164321 associated with asymmetry Group 4 (p=0.019). These results are confirmed by Principal Component Analysis (PCA) that showed three principal components explaining almost 80% of the variation seen in the studied group. PC1 and PC2 were associated with ESR1 SNP-rs3020318 (p<0.05). Diagnoses of disc displacement with reduction, masticatory muscle myalgia and arthralgia were highly prevalent in the asymmetry groups and all had strong statistical association to ENPP1 rs858339. The average JPF scores for asymmetric subjects before surgery (JPF=7), were significantly higher than symmetric subjects (JPF=2). Patients with asymmetry Group 3 reported the highest preoperative JPF scores and Group 2 and 3 were most likely to be cured of TMD one year after treatment. Conclusions PA cephalometrics can classify asymmetry into distinct groups; identify probability of TMD and genotype associations. Orthodontic and orthognathic treatment of facial asymmetry is very effective at eliminating TMD in most patients.

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Section: Discussionsupporting

confidence: 91%

ENPP1 and ESR1 genotypes associated with subclassifications of craniofacial asymmetry and severity of temporomandibular disorders

Chung

Richards

Nicot

et al. 2017

American Journal of Orthodontics and Dentofacial Orthopedics

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“…A second possibility is that SNPs in Enpp1 play an additional role, since Enpp1 polymorphisms are associated with differences in height, hip geometric indices and facial morphology. 28-30 …”

Section: Discussionmentioning

confidence: 99%

ACTN3 R577X genotypes associate with Class II and deepbite malocclusions

Zebrick

Teeramongkolgul

Nicot

et al. 2014

American Journal of Orthodontics and Dentofacial Orthopedics

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Introduction α-actinins are myofibril anchor proteins which influence contractile properties of skeletal muscle. ACTN2 is expressed in slow type I and fast type II fibers whereas ACTN3 is expressed only in fast fibers. ACTN3 homozygosity for the 577X stop codon (i.e. changing 577RR to 577XX - the R577X polymorphism) results in the absence of α-actinin-3 in about 18% of Europeans, diminished fast contractile ability, enhanced endurance performance and reduced bone mass or bone mineral density. We have examined ACTN3 expression and genetic variation in masseter muscle of orthognathic surgery patients to determine genotype associations with malocclusion. Methods Clinical information, masseter muscle biopsies and saliva samples were obtained from 60 subjects. Genotyping for ACTN3 SNPs, RT-PCR quantitation of muscle gene message and muscle morphometric fiber type properties were compared to determine statistical differences between genotype and phenotype. Results Muscle mRNA expression level was significantly different for ACTN3 SNP genotypes (p<0.01). The frequency of ACTN3 genotypes was significantly different for sagittal and vertical classifications of malocclusion with the clearest association being elevated 577XX genotype in skeletal class II malocclusion (p = 0.003). This genotype also resulted in significantly smaller diameter of fast type II fibers in masseter muscle (p = 0.002). Conclusion ACTN3 577XX is overrepresented in skeletal class II malocclusion, suggesting a biologic influence during bone growth. ACTN3 577XX is underrepresented in deep bite malocclusion, suggesting muscle differences contribute to variations in vertical facial dimensions.

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“…ENPP1 expression correlates with osteoblast differentiation, and osteoblast cultures overexpressing ENPP1 contain elevated amounts of PPi and show reduced mineral formation [14]. Ermakov et al [11] investigated the association of polymorphisms in the ENPP1 locus with normal variability of craniofacial phenotypes in 1,042 Western Eurasian individuals, and found that ENPP1 gene polymorphisms were associated with upper facial height. Additionally, associations were detected between head breadth and lower face height, and markers residing in or close to the promoter and 3′UTR of the ENPP1 gene.…”

Section: Discussionmentioning

confidence: 99%

“…ENPP1 (ectonucleotide pyrophosphatase/phosphodiesterase 1) encodes an enzyme that negatively regulates bone mineralization. When mutated at 5′UTR and 3′UTR, it leads to a change in the height of the upper face [11]. The GHR (growth hormone receptor) gene affects the normal growth and development of the human body.…”

Section: Introductionmentioning

confidence: 99%

“…The GHR (growth hormone receptor) gene affects the normal growth and development of the human body. Two GHR genetic variants, Pro561Thr (rs6184) and I526L (rs6180), have been shown to alter mandible height in an East Asian population [11]. FGFR1 (fibroblast growth factor receptor 1) affects normal facial morphology development in humans, and is associated with the cephalic index in multiple populations [11].…”

Section: Introductionmentioning

confidence: 99%

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Correlation between facial morphology and gene polymorphisms in the Uygur youth population

Zhang

et al. 2017

Oncotarget

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Human facial morphology varies considerably among individuals and can be influenced by gene polymorphisms. We explored the effects of single nucleotide polymorphisms (SNPs) on facial features in the Uygur youth population of the Kashi area in Xinjiang, China. Saliva samples were collected from 578 volunteers, and 10 SNPs previously associated with variations in facial physiognomy were genotyped. In parallel, 3D images of the subjects’ faces were obtained using grating facial scanning technology. After delimitation of 15 salient landmarks, the correlation between SNPs and the distances between facial landmark pairs was assessed. Analysis of variance revealed that ENPP1 rs7754561 polymorphism was significantly associated with RAla-RLipCn and RLipCn-Sbn linear distances (p = 0.044 and p = 0.012, respectively) as well as RLipCn-Stm curve distance (p = 0.042). The GHR rs6180 polymorphism correlated with RLipCn-Stm linear distance (p = 0.04), while the GHR rs6184 polymorphism correlated with RLipCn-ULipP curve distance (p = 0.047). The FGFR1 rs4647905 polymorphism was associated with LLipCn-Nsn linear distance (p = 0.042). These results reveal that ENPP1 and FGFR1 influence lower anterior face height, the distance from the upper lip to the nasal floor, and lip shape. FGFR1 also influences the lower anterior face height, while GHR is associated with the length and width of the lip.

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Family-based study of association between ENPP1 genetic variants and craniofacial morphology

Cited by 12 publications

References 45 publications

ENPP1 and ESR1 genotypes associated with subclassifications of craniofacial asymmetry and severity of temporomandibular disorders

ENPP1 and ESR1 genotypes associated with subclassifications of craniofacial asymmetry and severity of temporomandibular disorders

ACTN3 R577X genotypes associate with Class II and deepbite malocclusions

Correlation between facial morphology and gene polymorphisms in the Uygur youth population

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