Association Analysis Of Polymorphisms In OAS1 With Susceptibility And Severity Of Hand, Foot And Mouth Disease

Objective: To investigate the epidemiologic and clinical characteristics of Hand,foot and mouth Disease(HFMD) in Suzhou from 2010 to 2014. Analyze the relationship between four SNPs(Selectin P ligand-1 rs2228315,Scavenger receptor class B member 2 rs41284767, Interleukin-28 B rs12979860、O ligoadenylate synthetase 1 rs10774671) and the susceptibility and severity of HFMD. Methods: 1. Outpatient and inpatient children,s clinical and epidemiologic data with HFMD at the Children’s Hospital Affiliated to Soochow University was collected from 2010 to 2014. Enterovirus 71 and Coxsackie virus A 16 nucleic acid type were assayed by real-time fluorescence quantitative PCR. 2. A total of 333 cases of HFMD children agreed to participate in our study from Children’s Hospital Affiliated to Soochow University, 211 cases were male children and 122 cases were female children, 234 cases were mild children and 99 cases were severe children. Blood was collected from 163 control group children, and medical examinations were performed in the same period. These children did not have HFMD clinical symptoms and were healthy. DNA was extracted by a blood DNA kit. SNPs of SELPLG rs2228315、SCARB2 rs41284767、 IL28 B rs12979860 、OAS1rs10774671 were genotyped using Taq Man probe technology. SPSS 16.0 software was employed for statistic analysis. Results: 1. A total of 31205 HFMD cases were reported from 2010 to 2014. 2173 cases were severe. There was a significant difference in different years(P<0.001). HFMD is popular throughout the year from 2010 to 2014 in Suzhou. The peak months were from May to July each year. Male and female HFMD children were accounting for 61.71%, 38.29% of total cases from 2010 to 2014, respectively, and constituent ratio was 1.6:1. 1-4 years old children were most susceptible to HFMD, mainly concentrated at the age of 1-2 years old. Most of the patients appeared in Xiang C heng district, Wu Zhong district, Wu Jiang district, Hu Q iu district and Industrial Park district. 2. Nucleic acid testing positive cases were 2130 of hospitalized patient from 2010 to 2014. EV71 was 64.23%, CA16 was 35.78%. The positive rate of EV71 was higher than that of CA16 in severe HFMD,it was highest in 2011 while that of C A16 was highest in 2012. 3. EV71 infected HFMD children showed a longer duration of fever, milder oral mucosa and skin lesions, more frequency of the nervous system symptoms compared with CA16 infected HFMD children. The percentage of T cells(CD3+, CD3+CD4+, CD3+CD8+) was reduced, but the percentage of B cells(CD3-CD19+) increased in EV71 infected HFMD children compared with CA16 infected HFMD children(P<0.05). However, there was no significant difference in gender, age, total WBC count, NK cells percent, ALT, CK and CK-MB enzymes between EV71 infected HFMD children and CA16 infected HFMD children(P>0.05). 4. Nervous system symptoms were common in children with severe HFMD, CRP was decreased(P=0.028), LDH was increased(P=0.041). The level of IFN-γwas higher in mild group than in severe HFMD patients and control group(P=0.047). 5. SELPLG rs2228315 and SCARB2 rs41284767 SNPs had no relevance to susceptibility of HFMD caused by EV71 and CA16. 6. OAS1 rs10774671 and IL28 B rs12979860 had no correlation with the susceptibility of HFMD caused by EV71 and CA16. Children with the OAS1 rs10774671 genotype GG were susceptible to CA16 virus infection. There was a significant difference between severe and mild HFMD of the OAS1 rs10774671 genotype GG and AA+AG(P=0.013). The OAS1 rs10774671 genotype distribution had a correlation with gender(P=0.042). 7. The level of IFN-γ was higher in patients of OAS1 rs10774671 genotype GG than AA, AG. Conclusions: 1. The epidemiologic characteristics of HFMD had obvious difference in age, gender, region and season distribution, as well pathogen. The positive rate of EV71 was higher than that of CA16. 2. HFMD is popular throughout the year. Most of the cases were children less than 4 years old and there was a tendency of HFMD in boys. The peak months were from May to July. 3. The OAS1 rs10774671 genotype GG contributed to CA16 susceptib ility and was associated with development of mild HFMD.