Genetic and environmental factors associated with hypodontia

Introduction: Hypodontia, or tooth agenesis, is the most prevalent craniofacial malformation in humans. It may occur as part of a recognised genetic syndrome or as a non-syndromic isolated trait. Excluding third molars, the reported prevalence of hypodontia ranges from 1.6 to 6.9 %, depending on the population studied. Most affected individuals lack only one or two teeth, with permanent second premolars and upper lateral incisors the most likely to be missing. Both environmental and genetic factors are involved in the aetiology of hypodontia, with the latter playing a more significant role. Hypodontia individuals present a significant clinical challenge for orthodontists because the treatment time is prolonged and the treatment outcome is generally compromised. Hence, the identification of genetic and environmental factors may be particularly useful in the early prediction of this condition and the development of prevention strategies and novel treatments in the future. Objectives: The objectives of this study were two-fold: (1) to investigate the association between non-syndromic hypodontia and single nucleotide polymorphisms (SNPs) of candidate genes paired box 9 (PAX9), msh homeobox 1 (MSX1), axis inhibition protein 2 (AXIN2), and ectodysplasin A (EDA); and (2) to examine its association with environmental factors, such as exposure to smoking and alcohol during pregnancy. Materials and methods: Eighty-nine cases with two specific phenotypes were recruited: (1) individuals with one or more missing permanent lateral incisors; and (2) individuals with one or more missing permanent premolars. These cases were frequency-matched to 253 controls (patients with no missing teeth, excluding the third molars). Self-report data from both the participants and their mothers were collected, while DNA samples (in the form of blood or saliva) were collected from each participant. Both environmental and genetic data were analysed using conventional descriptive methods. Results: The sample had a mean chronological age of 16.6 years (SD=7.3), with most participants being female (59.6%), and of New Zealand European origin (75.4%). Using multiple logistic regression analyses, it was found that the T-allele of rs12853659 (EDA) was associated with a higher risk of hypodontia (odds ratio, OR = 2.79, P = 0.029), when adjusted for sex and ethnicity; and this was also true for the G-allele of rs2428151 (EDA), which was associated with a higher risk (OR = 2.87, P = 0.043). No statistically significant associations were found with the AXIN2 and MSX1 genes. Analysis of the environmental data revealed a significant association between hypodontia and maternal cigarette use during pregnancy (P < 0.01), as well as the number of cigarettes smoked per day (P < 0.05). To determine whether there was a biological gradient with cigarette smoking during pregnancy, maternal cigarette consumption per day was divided into three groups: none, 1 to 9, and 10 or more. A dose-response association was observed (OR = 2.05 (0.73-5.75), P = 0.232; OR = 4.18 (1.49-11.80), P = 0.007, respectively). These findings suggest that greater cigarette smoking during pregnancy resulted in higher odds of having a child with hypodontia. There were no statistically significant differences between the case and control groups in any of the other environmental factors investigated (that is, alcohol and caffeine consumption). Conclusions: Hypodontia is a complex condition that is influenced by both genetic and environmental factors. The present study reveals some evidence that polymorphisms of the EDA and PAX9 genes are associated with specific phenotypes of non-syndromic hypodontia. Furthermore, this study is the first to date to test the association between maternal cigarette smoking during pregnancy and having a child with hypodontia. The observed biological gradient strongly suggests an association between tobacco smoking and this dental anomaly. However, larger samples are needed to investigate the association further, as well as to confirm the genetic variants associated with hypodontia

Genetic and environmental factors associated with hypodontia

Introduction: Hypodontia, or tooth agenesis, is the most prevalent craniofacial malformation in humans. It may occur as part of a recognised genetic syndrome or as a non-syndromic isolated trait. Excluding third molars, the reported prevalence of hypodontia ranges from 1.6 to 6.9 %, depending on the population studied. Most affected individuals lack only one or two teeth, with permanent second premolars and upper lateral incisors the most likely to be missing. Both environmental and genetic factors are involved in the aetiology of hypodontia, with the latter playing a more significant role. Hypodontia individuals present a significant clinical challenge for orthodontists because the treatment time is prolonged and the treatment outcome is generally compromised. Hence, the identification of genetic and environmental factors may be particularly useful in the early prediction of this condition and the development of prevention strategies and novel treatments in the future. Objectives: The objectives of this study were two-fold: (1) to investigate the association between non-syndromic hypodontia and single nucleotide polymorphisms (SNPs) of candidate genes paired box 9 (PAX9), msh homeobox 1 (MSX1), axis inhibition protein 2 (AXIN2), and ectodysplasin A (EDA); and (2) to examine its association with environmental factors, such as exposure to smoking and alcohol during pregnancy. Materials and methods: Eighty-nine cases with two specific phenotypes were recruited: (1) individuals with one or more missing permanent lateral incisors; and (2) individuals with one or more missing permanent premolars. These cases were frequency-matched to 253 controls (patients with no missing teeth, excluding the third molars). Self-report data from both the participants and their mothers were collected, while DNA samples (in the form of blood or saliva) were collected from each participant. Both environmental and genetic data were analysed using conventional descriptive methods. Results: The sample had a mean chronological age of 16.6 years (SD=7.3), with most participants being female (59.6%), and of New Zealand European origin (75.4%). Using multiple logistic regression analyses, it was found that the T-allele of rs12853659 (EDA) was associated with a higher risk of hypodontia (odds ratio, OR = 2.79, P = 0.029), when adjusted for sex and ethnicity; and this was also true for the G-allele of rs2428151 (EDA), which was associated with a higher risk (OR = 2.87, P = 0.043). No statistically significant associations were found with the AXIN2 and MSX1 genes. Analysis of the environmental data revealed a significant association between hypodontia and maternal cigarette use during pregnancy (P < 0.01), as well as the number of cigarettes smoked per day (P < 0.05). To determine whether there was a biological gradient with cigarette smoking during pregnancy, maternal cigarette consumption per day was divided into three groups: none, 1 to 9, and 10 or more. A dose-response association was observed (OR = 2.05 (0.73-5.75), P = 0.232; OR = 4.18 (1.49-11.80), P = 0.007, respectively). These findings suggest that greater cigarette smoking during pregnancy resulted in higher odds of having a child with hypodontia. There were no statistically significant differences between the case and control groups in any of the other environmental factors investigated (that is, alcohol and caffeine consumption). Conclusions: Hypodontia is a complex condition that is influenced by both genetic and environmental factors. The present study reveals some evidence that polymorphisms of the EDA and PAX9 genes are associated with specific phenotypes of non-syndromic hypodontia. Furthermore, this study is the first to date to test the association between maternal cigarette smoking during pregnancy and having a child with hypodontia. The observed biological gradient strongly suggests an association between tobacco smoking and this dental anomaly. However, larger samples are needed to investigate the association further, as well as to confirm the genetic variants associated with hypodontia

Hypodontia: An Update on Its Etiology, Classification, and Clinical Management

Hypodontia, or tooth agenesis, is the most prevalent craniofacial malformation in humans. It may occur as part of a recognised genetic syndrome or as a nonsyndromic isolated trait. Excluding third molars, the reported prevalence of hypodontia ranges from 1.6 to 6.9%, depending on the population studied. Most affected individuals lack only one or two teeth, with permanent second premolars and upper lateral incisors the most likely to be missing. Both environmental and genetic factors are involved in the aetiology of hypodontia, with the latter playing a more significant role. Hypodontia individuals often present a significant clinical challenge for orthodontists because, in a number of cases, the treatment time is prolonged and the treatment outcome may be compromised. Hence, the identification of genetic and environmental factors may be particularly useful in the early prediction of this condition and the development of prevention strategies and novel treatments in the future