Association among Oral Health,Apical Periodontitis,CD14 Polymorphisms,and Coronary Heart Disease in Middle-aged Adults

Introduction

There is evidence to suggest that an association exists between oral infections and coronary heart disease (CHD). Subjects presenting lesions of endodontic origin (LEOs) or pulpal inflammation had an increased risk of developing CHD. However, findings concerning systemic manifestations of apical periodontitis (AP) remain controversial. An association between CD14 gene polymorphisms and atherosclerosis-associated diseases has been shown, but there are no data regarding an association between CD14 polymorphism and AP. This study evaluated associations between clinical oral health status, CD14 polymorphisms, and CHD.

Methods

A case-controlled clinical trial was designed to compare middle-aged adults with acute myocardial infarction or unstable angina (n = 51) within 12 months of the acute event defined as first manifestation with healthy controls (n = 49). Participants were matched for age, sex, and socioeconomic status. Indicators of oral disease and compliance were evaluated. CD14 polymorphisms were analyzed by restriction fragment length polymorphism–polymerase chain reaction.

Results

CHD subjects had a higher prevalence of oral diseases and lower compliance to oral preventive strategies than healthy controls. Multivariate analysis showed a positive association between missing teeth (odds ratio [OR] = 1.37; 95% confidence interval [CI], 1.02–1.85), the number of LEOs (OR = 4.37; 95% CI, 1.69–11.28), chronic periodontitis (OR = 5.87; 95% CI, 1.17–29.4), and CHD. No statistically significant association emerged between the CD14 C(−260)T and the CD14 C(−159)T polymorphism, endodontic or periodontal disease, and CHD.

Conclusions

Chronic oral diseases may increase the risk of CHD and may be an unconventional risk factor for CHD.     

Association of common variants in PAH and LAT1 with non-syndromic cleft lip with or without cleft palate (NSCL/P) in the Polish population

Background

Non-syndromic cleft lip with or without cleft palate (NSCL/P) is a common structural malformation with a complex and multifactorial aetiology. Associations of abnormalities in phenylalanine metabolism and orofacial clefts have been suggested.

Methods

Eight single nucleotide polymorphisms (SNPs) of genes encoding phenylalanine hydroxylase (PAH) and large neutral l-amino acid transporter type 1 (LAT1), as well as the PAH mutation that is most common in the Polish population (rs5030858; R408W), were investigated in 263 patients with NSCL/P and 270 matched controls using high resolution melting curve analysis (HRM).

Results

We found that two polymorphic variants of PAH appear to be risk factors for NSCL/P. The odds ratio (OR) for individuals with the rs7485331 A allele (AC or AA) compared to CC homozygotes was 0.616 (95% confidence interval [CI] = 0.437–0.868; p = 0.005) and this association remains statistically significant after multiple testing correction. The PAH rs12425434, previously associated with schizophrenia, was borderline associated with orofacial clefts. Moreover, haplotype analysis of polymorphisms in the PAH gene revealed a 4-marker combination that was significantly associated with NSCL/P. The global p-value for a haplotype comprised of SNPs rs74385331, rs12425434, rs1722392, and the mutation rs5030858 was 0.032, but this association did not survive multiple testing correction.

Conclusion

This study suggests the involvement of the PAH gene in the aetiology of NSCL/P in the tested population. Further replication will be required in separate cohorts to confirm the consistency of the observed association.     

Polymorphism of the CD14 and TLR4 Genes and Post-treatment Apical Periodontitis

Introduction

This study investigated the association of CD14 -260C>T and TLR4 +896A>G gene polymorphisms with post-treatment apical periodontitis in Brazilian individuals.

Methods

The study population consisted of 41 patients with post-treatment apical periodontitis and 42 individuals with root canal–treated teeth exhibiting healed/healing periradicular tissues (controls). All teeth had apical periodontitis lesions at the time of treatment, which was completed at least 1 year previously. Saliva was collected from the participants; DNA was extracted and used for CD14 and TLR4 genotyping using the polymerase chain reaction–restriction fragment length polymorphism approach and a real-time polymerase chain reaction TaqMan assay (Applied Biosystems, Foster City, CA), respectively.

Results

No specific genotype or allele of the CD14 and TLR4 genes or any combination thereof was positively associated with post-treatment apical periodontitis (P > .05).

Conclusions

Data from the present study suggest that polymorphisms in the CD14 and TLR4 genes do not influence the response to endodontic treatment of teeth with apical periodontitis.     

Association of Wnt3A gene variants with non-syndromic cleft lip with or without cleft palate in Chinese population

Objective

Non-syndromic cleft lip with or without cleft palate (NSCLP) is one of the most common birth defects all over the world. Both genetic and environmental factors may contribute to NSCLP. Recent studies have demonstrated that Wnt/β-catenin signalling pathway is required for lip and palate formation. WNT family may play an important role in the development of NSCLP. This study aimed to evaluate the association between Wnt3A gene polymorphisms and NSCLP in Chinese population from Northwest China.

Design

216 patients with NSCLP and 233 normal controls were genotyped for two SNPs of Wnt3A by PCR-RFLP. Both SNPs genotype frequencies were analysed between cases group and controls group.

Results

The frequencies of rs752107 TT and rs3121310 AA were significantly higher in NSCLP cases group (7.4%, 15.3%) than that in controls group (2.1%, 9.5%) with p-value = 0.013, 0.014, corrected p value (p-corr) <0.05 and with odds ratio (OR) = 3.49, 95% confidence interval [CI]: 1.244–9.79, OR = 2.27, 95% CI: 1.17–4.38, respectively; the frequency of rs3121310 GA was also higher in NSCLP cases group (57.4%) than in controls group (52.0%) with p-value = 0.042 and OR = 1.56 (95% CI: 1.02–2.39). And the frequency of rs752107 TT of Wnt3A showed higher risk in female patients, while the frequency of A allele of rs3121310 showed stronger association in male patients.

Conclusions

This is the first report that two SNPs of Wnt3A (rs752107 and rs3121310) are significantly associated with NSCLP in Chinese population. These findings provide a context for understanding the genetic aetiology of NSCLP.     

Polymorphic variants of genes related to arginine metabolism and the risk of orofacial clefts

Objective

Maternal mid-pregnancy low levels of symmetric dimethylarginine and newborn low levels of citrulline are suspected to be risk factors for orofacial clefts. This study was undertaken to investigate the involvement of polymorphic variants of genes related to arginine metabolism in the susceptibility of clefting.

Design

PCR-RFLP and HRM analyses were used to analyze single nucleotide polymorphisms (SNPs) of ASS1, ASL, and SLC25A13 in 172 children with non-syndromic cleft lip with or without cleft palate (CL/P) and 188 controls without congenital anomalies. The differences in allele and genotype frequencies between cases and controls were determined using standard Chi-square and Fisher exact tests. The odds ratio (OR) and associated 95% confidence intervals (95% CI) for individuals with CL/P versus controls were also calculated. Associations between the investigated polymorphisms and the risk of being born with an orofacial cleft were tested using the nonparametric and genetic model-free Multifactor Dimensionality Reduction (MDR) approach.

Results

Analysis of five SNPs of the ASS1 gene revealed that the G allele of rs7860909 is associated with increased CL/P risk. Compared to individuals with the AA genotype, the G allele carriers had an OR of 1.768 (95% CI: 1.133-2.759; p = 0.012). For the remaining SNPs of all analysed genes, there was no overall evidence for cleft association considering the allele and genotype distribution. However, gene-by-gene interaction analysis conducted using the MDR approach revealed a significant interactive genetic effect of ASS1 (rs666174) and SLC25A13 (rs10252573) on the occurrence of clefting (p = 0.002).

Conclusion

Our results demonstrate moderate evidence for the association of polymorphic variants of genes related to arginine metabolism with abnormal palatogenesis.     

Association of IL1 gene polymorphisms with chronic periodontitis in Brazilians

Chronic periodontal disease (PD) is an infectious immune-inflammatory illness. Polymorphisms in IL1 genes play a role in inflammatory diseases through the modulation of cytokine levels.

Objective

This study aimed to investigate the association between polymorphisms in the IL1 gene cluster and chronic periodontitis in a Brazilian population.

Design

A sample of 113 subjects over 25 years (mean age 41.2) were grouped into: 44 healthy individuals, 31 subjects with moderate and 38 with severe periodontitis. DNA was obtained through a mouthwash and oral mucosa scraping. PCR-RFLP was used to identify the following polymorphisms: IL1A C − 889T (rs1800587), IL1B C − 511T (rs16944), IL1B C + 3954T (rs11436340), IL1RN intron 2 (rs2234663). Differences in the allele/genotype/haplotype frequencies were assessed by Chi-square test (p < 0.05). The risk associated with alleles, genotypes and haplotypes was calculated as odds ratio (OR) with 95% confidence intervals (CI).

Results

Neither IL1A (C − 889T) nor IL1B (C + 3954T) polymorphisms was associated with chronic PD. Allele T for IL1B (C − 511T) only associated with PD in the group of blacks and mulattos. Moreover, genotype 2/2 for IL1RN (intron 2) was associated with severe PD.

Conclusions

Genotype 2/2 of IL1RN for the whole Brazilian population and allele T of IL1B (C − 511T) in a subgroup of Afro-Americans and mulattos were suggested as putative risk indicators for chronic periodontitis.     

Association of vdr,cyp27b1, cyp24a1 and mthfr gene polymorphisms with oral lichen planus risk

Objectives

The current study investigated the association between VDR EcoRV (rs4516035), FokI (rs2228570), ApaI (rs7975232) and TaqI (rs731236), CYP27B1 (rs4646536), CYP24A1 (rs2296241), and MTHFR (rs1801133) gene polymorphisms and risk of oral lichen planus (OLP) occurrence.

Materials and methods

The study group consisted of 65 oral lichen planus patients and 100 healthy blood donors in the control group. Single nucleotide polymorphisms were genotyped by real time PCR or PCR-restriction fragment length polymorphism (RFLP) method.

Results

Heterozygous as well as mutated genotype of vitamin D receptor (VDR) FokI (rs2228570) polymorphism was associated with increased oral lichen planus risk in comparison with wild type genotype (odds ratio (OR) = 3.877, p = 0.017, OR = 38.153, p = 0.001, respectively). A significantly decreased OLP risk was observed for heterozygous genotype of rs2296241 polymorphism in CYP24A1 gene compared with the wild type form (OR = 0.314, p = 0.012). VDR gene polymorphisms ApaI and TaqI were in linkage disequilibrium (D’ = 0.71, r ² = 0.22). Identified haplotype AT was associated with decreased OLP risk (OR = 0.592, p = 0.047).

Conclusion

Our results highlight the possible important role of VDR FokI (rs2228570) and CYP24A1 rs2296241 gene polymorphisms for oral lichen planus susceptibility.

Clinical relevance

Identification of new molecular biomarkers could potentially contribute to determination of individuals with OLP predisposition.

     

High HIF-1α expression genotypes in oral lichen planus

Objective

The aim of this study is to assess whether C1772T and G1790A hypoxia-inducible factor-1 (HIF-1)α polymorphisms are associated with risk of oral lichen planus (OLP).

Material and methods

Restriction fragment length polymorphism analysis was used to investigate HIF-1α C1779T and G1790A polymorphisms in 32 OLP and 88 individuals without OLP.

Results

The frequency of the CC, TT, GA, and AA genotypes was higher in patients with OLP. Notably, individuals carrying the C and A, and T and A haplotypes showed a significant association OLP risk.

Conclusions

Our study demonstrated that the C1772T and G1790A polymorphisms of HIF-1α gene increased the risk of OLP. C1772T and G1790A polymorphisms of HIF-1α gene had differing patterns of allelic imbalance in the normal samples and subsequent chronic lesions. Further studies are necessary to elucidate the HIF-1α pathway in OLP, which would facilitate the development of novel therapeutic strategies for the prevention and treatment of OLP.

Clinical relevance

These results, in conjunction with previous studies, suggest that HIF-1α may play important roles in the chronicity of oral mucosa lesions of OLP patients. Taken together, we suggest that HIF-1α polymorphisms enhance its target genes, thereby altering the microenvironment and supporting sequential release of inflammatory mediators or cellular events in OLP. It appears unlikely that inhibition of a single proinflammatory mediator will prove useful in clinical practice, but several ways to reprogram mediators engaged in a wide array of roles simultaneously are encouraging.     

Association between genetic risk score and periodontitis onset and progression: a pilot study

Aim

Recent research has focused attention on the single nucleotide polymorphisms (SNPs) involved in the host response in periodontitis. However, so as to combine the relatively small effects of individual genes the use of multi locus genetic risk (GRS) has been proposed. This study aims to evaluate whether the genetic risk score may predict periodontitis onset and progression.

Materials and methods

Fifty patients were divided into various groups according to periodontal status. Total DNA was isolated from epithelial oral cells by a masked operator and the selected SNPs were analysed. A GRS was calculated using an additive model.

Results

We found a strong association only between TNF rs1800629 and diffused forms of periodontitis. Data show that GRS is able to discriminate diffused forms of periodontitis from localized ones. Finally, a progressive increase of the GRS is evident in advanced periodontitis in comparison with early forms.

Discussion

In recent years, research on genetic polymorphism has had limited success in predicting the susceptibility to periodontal disease. However, our results indicate that the use of the genetic risk score could be promising. Further studies are necessary to include data from multiple genes so as to confirm our result.     

Identification of SNP markers on 1p36 and association analysis of EPB41 with mandibular prognathism in a Chinese population

Objective

The results of a genome-wide scan suggested that chromosome locus 1p36 might be linked to the etiology of mandibular prognathism (MP) amongst Asian ethnicities. In this study, we performed a two-stage case-control association study to determine whether one or more genes that confer susceptibility to MP are located within this genomic region.

Design

In the first stage of the study, we examined 103 single nucleotide polymorphisms (SNPs) on 1p36 across an 8.6 Mb critical region and within four candidate genes in 158 cases and 147 controls to identify genes associated with MP. In the second stage of the study, we examined an additional 23 SNPs within the erythrocyte membrane protein band 4.1 (EPB41) gene in 211 cases and 224 controls.

Results

Four SNPs located in the EPB41 gene showed possible allelic and genotypic associations with MP (P < 0.03 and P < 0.05, respectively) in the first stage. In the analysis of single SNPs in the second stage, the allele of rs4654388 showed the strongest significant association with MP (P = 0.008) and the rs4654388 G-allele was associated with a significantly increased risk of MP (OR: 1.78, 95% CI: 1.16-2.74). Haplotype analysis revealed that MP was associated significantly with haplotype GTTCAGGT (P_corrected = 0.031), which included the rs4654388 G-allele.

Conclusions

An association between genetic polymorphisms in the EPB41 gene and MP has been observed. Although the polymorphisms which may contribute to MP have not been determined, the results of our study suggest that the EPB41 gene could confer susceptibility to MP.     

Interaction between tumour necrosis factor-α gene polymorphisms and substance use on risk of betel quid-related oral and pharyngeal squamous cell carcinoma in Taiwan

Objective

Betel quid (BQ) components induce the secretion of tumour necrosis factor-alpha (TNF-α) in oral keratinocytes, which promotes oral mucosal inflammation and oral cancer. This study was carried out to evaluate the association of TNFA genetic variants (−308G>A and −238G>A) with the risk and prognosis of BQ-related oral and pharyngeal squamous cell carcinoma (OPSCC).

Design

A total of 403 subjects (205 cancer cases and 198 healthy controls) who habitually chewed BQ were recruited. The genotypes were determined by TaqMan real-time assays.

Results

G allele and G/G genotype at TNFA −308 were associated with a 1.95-fold (95%CI: 1.16–3.28, p_corrected = 0.024) and 2.28-fold (95%CI: 1.30–4.00, p_corrected = 0.008) increased risk of cancer as compared to those with A allele or A/A + A/G genotypes, respectively. In addition, G allele (p = 0.080) and G/G genotype (p = 0.076) at TNFA −238 were associated with a borderline but statistically significant increased risk of OPSCC. The combined G/G + G/G genotype at both loci had a 2.37-fold increased risk of OPSCC as compared to those with other combined genotypes (95%CI: 1.41–4.00, p = 0.001). Interactions between combined genotypes and smoking status were also found to contribute to risk of BQ-related OPSCC. There was no association of TNFA genotypes with clinicopathologic findings or the survival of OPSCC patients.

Conclusions

BQ-chewers who carry the G allele or G/G genotype in TNFA −308 may have an increased risk of OPSCC. The intensity of cigarette smoking modulates the effect of the combined TNFA genotypes on risk of BQ-related OPSCC.     

Polymorphism of the FcγRIIIa gene and post-treatment apical periodontitis

Introduction

Polymorphisms of genes encoding leukocyte surface receptors for the constant region of immunoglobulin G (FcγR) might influence the host response to infection and consequently affect the outcome of the endodontic treatment. This study investigated the association of FcγRIIIa gene (FcγRIIIA) polymorphism with post-treatment apical periodontitis in Brazilian subjects.

Methods

The study population consisted of 26 patients with post-treatment apical periodontitis and 43 subjects with root canal–treated teeth exhibiting healthy/healing periradicular tissues (controls). All teeth had apical periodontitis lesions at the time of treatment, which was completed at least 1 year previously. Saliva was collected from the participants; DNA was extracted and used for FcγRIIIA genotyping.

Results

No significant associations were found between any specific genotype of FcγRIIIA (P = .63) or allele (P = .76) and post-treatment apical periodontitis. Overall, the most prevalent allele in the study population was FcγRIIIA-F158 (68.8%). The genotype V/F was the most common among the population, occurring in 50.7% of the subjects.

Conclusions

Data from the present study suggest that polymorphism in the FcγRIIIa does not influence the patient’s response to endodontic treatment of teeth with apical periodontitis.     

Types of External Root Resorption of Replanted Teeth: Analysis of the Clinical Aspects and of Interleukin-4 Gene Polymorphisms Involvement

Introduction

The absence or presence of root resorption on the surface of a replanted tooth indicates an immune-inflammatory reaction. Recent research even suggests the participation of host predominant immunologic profile on types of resorptions detected on the root surface. Because interleukin 4 (IL-4) is an important anti-inflammatory cytokine, this study aimed to investigate the association of clinical variables and polymorphisms in IL4 with types of resorption of replanted teeth after 1 year of follow-up.

The role of genetic factors in the etiology of temporomandibular disorders: a review

Objectives: To perform a review of the literature of published articles assessing the role of genetic factors in the etiology of temporomandibular disorders (TMDs).

Methods: A PubMed search was carried out by looking for all controlled clinical trials related to the topic and limiting the search to English language and humans. The references from the studies included and those from review articles were also examined for further relevant papers.

Results: A total of 1999 articles were first identified, 24 of which were considered relevant to the topic. Two other papers were found while searching the references. While TMD signs and symptoms’ co-occurrence was not found in subjects within the same family, many gene polymorphisms were shown to be associated with a higher or lower risk of TMD. Such genes were mainly related to serotonin activity and metabolism, Tcellreceptor pathway, catecholamine activity and metabolism, estrogen activity, folate metabolism, glutathione activity, ANKH gene, major histocompatibility complex, extracellular matrix metabolism, genes studied in the orofacial pain prospective evaluation risk and assessment (OPPERA) study, and related to cytokines activity and metabolism.

Discussion: This new understanding of the pathophysiology of TMD can lead to a different treatment approach by identifying the subjects at higher risk for this pathology, and possibly by creating new drugs targeted at interfering with the expression of the genes that enhance such risk.     

Urease activity in dental plaque and saliva of children during a three-year study period and its relationship with other caries risk factors

Bacterial urease activity in dental plaque and in saliva generates ammonia, which can increase the plaque pH and can protect acid-sensitive oral bacteria. Recent cross-sectional studies suggest that reduced ability to generate ammonia from urea in dental plaque can be an important caries risk factor. In spite of this proposed important clinical role, there is currently no information available regarding important clinical aspects of oral ureolysis in children.

Objective

The objective of this study was to evaluate the distribution and pattern of urease activity in the dental plaque and in the saliva of children during a three-year period, and to examine the relationship of urease with some important caries risk factors.

Methods

A longitudinal study was conducted with repeated measures over a three-year period on a panel of 80 children, aged 3–6 years at recruitment. The dynamics of change in urease activity were described and associated with clinical, biological, and behavioural caries risk factors.

Results

Urease activity in plaque showed a trend to remain stable during the study period and was negatively associated with sugar consumption (P < 0.05). Urease activity in unstimulated saliva increased with age, and it was positively associated with the levels of mutans streptococci in saliva and with the educational level of the parents (P < 0.05).

Conclusions

The results of this study reveal interesting and complex interactions between oral urease activity and some important caries risk factors. Urease activity in saliva could be an indicator of mutans infection in children.     

Prevalence of dentine hypersensitivity and study of associated factors: A European population-based cross-sectional study

Objectives

Dentine hypersensitivity (DH) manifests as a transient but arresting oral pain. The incidence is thought to be rising, particularly in young adults, due to increases in consumption of healthy, yet erosive, diets. This study aimed to assess the prevalence of DH and relative importance of risk factors, in 18–35 year old Europeans.

Methods

In 2011, 3187 adults were enrolled from general dental practices in France, Spain, Italy, United Kingdom, Finland, Latvia and Estonia. DH was clinically evaluated by cold air tooth stimulation, patient pain rating (yes/no), accompanied by investigator pain rating (Schiff 0–3). Erosive toothwear (BEWE index 0–3) and gingival recession (mm) were recorded. Patients completed a questionnaire regarding the nature of their DH, erosive dietary intake and toothbrushing habits.

Results

41.9% of patients reported pain on tooth stimulation and 56.8% scored ≥1 on Schiff scale for at least one tooth. Clinical elicited sensitivity was closely related to Schiff score and to a lesser degree, questionnaire reported sensitivity (26.8%), possibly reflecting the transient nature of the pain, alongside good coping mechanisms. Significant associations were found between clinically elicited DH and erosive toothwear and gingival recession. The questionnaire showed marked associations between DH and risk factors including heartburn/acid reflux, vomiting, sleeping medications, energy drinks, smoking and acid dietary intake.

Conclusion

Overall, the prevalence of DH was high compared to many published findings, with a strong, progressive relationship between DH and erosive toothwear, which is important to recognise for patient preventive therapies and clinical management of DH pain.     

Intake of dairy products and the prevalence of dental caries in young children

Objectives

In vitro studies show that milk or milk components may have cariostatic properties. However, the results of epidemiological studies on the association between intake of dairy products and dental caries have been inconsistent. The purpose of this cross-sectional study was to examine the association between intake of dairy products and the prevalence of dental caries in young children.

Methods

Study subjects were 2058 Japanese children aged 3 years. Information on diet was assessed with a self-administered brief diet history questionnaire for children. The consumption of dairy products was categorized into 3 levels in order to represent the tertiles as closely as possible. Dental caries was assessed by a visual examination. Adjustment was made for sex, toothbrushing frequency, use of fluoride, between-meal snack frequency, maternal smoking during pregnancy, environmental tobacco smoke exposure at home, and paternal and maternal educational levels.

Results

Compared with yogurt consumption at the lowest tertile (<1 time/week), its intake at the highest level (≥4 times/week) was significantly associated with a lower prevalence of dental caries, showing a clear dose–response relationship (adjusted prevalence ratio = 0.78, 95% confidence interval: 0.62–0.98, P for trend = 0.04). There were no material associations between intake of cheese, bread and butter, or milk and the prevalence of dental caries.

Conclusions

These data suggest that a high consumption of yogurt may be associated with a lower prevalence of dental caries in young children.     

The 19-bp deletion polymorphism of dihydrofolate reductase (DHFR) and nonsyndromic cleft lip with or without cleft palate: evidence for a protective role

Objective

Nonsyndromic cleft lip with or without cleft palate (NS-CL/P) are among the most common congenital birth defects worldwide. Several lines of evidence point to the involvement of folate, as well as folate metabolizing enzymes in risk reduction of orofacial clefts. Dihydrofolate reductase (DHFR) enzyme participates in the metabolic cycle of folate and has a crucial role in DNA synthesis, a fundamental feature of gestation and development. A functional polymorphic 19-bp deletion within intron-1 of DHFR has been associated with the risk of common congenital malformations. The present study aimed to evaluate the possible association between DHFR 19-bp deletion polymorphism and susceptibility to NS-CL/P in an Iranian population.

Material and Methods

The current study recruited 100 NS-CL/P patients and 100 healthy controls. DHFR 19-bp deletion was determined using an allele specific-PCR method.

Results

We observed the DHFR 19-bp homozygous deletion genotype (D/D) vs. homozygous wild genotype (WW) was more frequent in controls than in NS-CL/P patients (25% vs. 13%), being associated with a reduced risk of NS-CL/P in both codominant (OR=0.33, P=0.027) and recessive (OR=0.45, P=0.046) tested inheritance models. We also stratified the cleft patients and reanalyzed the data. The association trend for CL+CL/P group compared to the controls revealed that the DD genotype in both codominant (OR=0.30, P=0.032) and recessive models (OR=0.35, P=0.031) was associated with a reduced risk of CL+CL/P.

Conclusions

Our results for the first time suggested the DHFR 19-bp D/D genotype may confer a reduced risk of NS-CL/P and might act as a protective factor against NS-CL/P in the Iranian subjects.