Study participants
125 Chinese patients with RAU (mean age ± SD = 39.5 ± 12.9 years) were recruited, 62 was men and 63 was women, 6 were smokers. All subjects were assessed by an oral medicine specialist, the presence of aphthous ulcers were confirmed by them.
Blood samples were also obtained from 116 age and sex-matched healthy Chinese controls. Their RAU status confirmed by medical records and inquiries of patients, there is still possible that a small proportion subjects suffered from RAU. This might weaken the identified strength of associations. In our study, only six smokers were recruited to the patient group while 10 smokers were recruited in healthy control, which make it impossible to evaluate the effect of smoking on any gene associations.
The detailed demographic characteristics of the study population was listed in Table 1. Statistical analysis showed there was no significant difference in age, gender, BMI and smoking between the two groups, which indicated that enrolled subject from two groups matched in the current study. However, it seems that alcohol drinking could increase the risk of RAU occurrence (P=0.032, table 1).
A allele of rs2275913 and C allele of rs763780 raise the risk of RAU
The distributions of each genotype and allele from SNP sites are shown in Table 2, and their distribution complied with Hardy-Weinberg equilibrium. As for the genotype and allele distribution in rs2275913, a significant difference was observed between healthy control and RAU patients (Table 2). In addition, AA genotype carrier had remarkably increased risks of RAU occurrence compared with genotype GG (P < 0.05). Moreover, A allele carrier had higher risk on RAU occurrence compared with G allele carriers (OR, 1.1192; 95% CI, 1.012–1.404; p = 0.037). In addition, data from table 2 also indicated the AA genotype and A allele were substantially distributed in female population (P<0.05), instead of male sub-population (p>0.05, Table 2).
We also observed similar results about rs763780 polymorphism. There was a significant difference in the genotype and allele frequencies between RAU patients and control subjects, as demonstrated in Table 2. In addition, C allele rather than T allele increases the risk of developing RAU (Table 2). Furthermore, our study indicated that C allele caused higher risk than in T allele in female subgroup (P=0.004). However, in the male sub-population, the CC genotype did not cause significant change of RAU risk ratio, as well as C allele.
IL-17 polymorphism is related to RAU severity
RAU severity was evaluated based on number of lesions in one patient. In the current study, we classified into two sub-groups, less than three lesions and ≥ three lesions in RAU patients. The distribution of SNP among RAU severity was listed in Table 3. Results showed there was a significant difference between all the genotypes and alleles in different severity-groups, which suggests that these two IL-17 polymorphisms are risk factors for RAU severity.
Serum IL-17A/F levels are higher in RAU patients
The average serum IL-17A concentration was 2.38 ± 0.14 pg/ mL and 4.31±0.27 pg/ mL in healthy controls and RAU patients, respectively (Table 1). IL-17A serum levels in RAU patients were higher than healthy controls (P=0.0221, Table 1). The serum levels of IL-17F in RAU patients were significantly higher compared with healthy subjects (P=0.0314, Table 1). Further, f of in each genotype, there was significant difference of serum IL-17A and IL-17F concentration among all three genotypes about these two genic loci (Table 4), which indicated that A allele in rs2275913 and C allele in rs763780 possibly increased the IL17A and IL17F secretion respectively in RAU patients.