The Study Of The Polymorphism Of Beta-1 Adrenergic Receptor Gene Located In 1165 In Children With Hand-foot-mouth Disease Infected By EV71

Objective: To study the levels of adrenaline and norepinephrine in the severe hand,foot and the mouth disease(HFMD)infected by EV71,and the single nucleotide polymorphism of β1-adrenergic receptor located in 1165,as well as the relationship between gene polymorphism,epinephrine and norepinephrine.The pathogenesis of HFMD and the early warning index of HFMD were investigated from the point of view of gene.Methods: The object of study were enrolled from October 2015 to September 2016 of the Pediatric Ward and Child Care Center in Maternal and Child Health Care Hospital of Hainan Province(Hainan Provincial Children’s Hospital).The β1-adrenergic receptor located in 1165 was analyzed by PCR and Sanger sequencing.Plasma adrenaline and norepinephrine levels were measured by enzyme linked immunosorbent assay(ELISA).The method of the normal data and the variance homogeneity was based on the independent sample t test method,and the rank sum test method was used for the measurement data that did not obey the normal distribution.The count data was compared using the R * C table test method.Results:(1)To compare the clinical characteristics of the HFMD infected by EV71 and healthy children: There were 81 cases of HFMD infected by EV71,including 57 cases of male children,24 cases of female children,age(2.2 ± 1.1)years old.Including 22 cases of mild HFMD and 59 cases of severe HFMD.A total of 66 healthy children,including 31 cases of male children,35 female children,age(2.9 ± 1.1)years old.There was no significant difference in distribution of sex and age between EV71 infection group and control group.In the HFMD patients infected by EV71,there were no statistically difference between the mild group and the severe group in sex,age,erythrocyte sedimentation rate,procalcitonin,alanine aminotransferase,total protein,albumin,globulin,creatine kinase isoenzyme,lactate dehydrogenase,serum sodium,serum potassium and serum calcium.While white blood cells,aspartate aminotransferase in severe HFMD was significantly higher than that in mild HFMD(P <0.05).(2)Analysis the β1 adrenergic receptor located in 1165 genotype of 66 healthy children: The frequencies of GG,GC and CC genotypes were 7%,41%,52%,respectively,and the allele frequencies of G and C were 28% and 72%,respectively.there was no significant gender difference in the genotype and allele frequency distribution on β1-adrenergic receptor located in 1165(P> 0.05).(3)To analyze the genotype of β1 adrenergic receptor located in 1165 in 81 cases HFMD patients infencted in EV71.Genotype frequencies were GG11%,GC42%,CC47%,G,C allele frequencies were 32% and 68%,respectively.There was no gender difference in genotype and allele of β1 adrenergic receptor located in 1165.There was no significant difference in the genotype frequencies between the EV71 infection group and the control group(χ2=0.644,P>0.05).As well as in the allele frequencies(χ2= 0.570,P>0.05).Further analysis of the severity of the disease showed that there were no significant differences in genotype and allele frequency between the light group and the severe group(genotype frequencies =3.654,P>0.05,allele frequencies =3.565,P >0.05).(4)To detect the level of adrenaline and norepinephrine in the plasma of the HFMD patient infected by EV71.The level of adrenaline in plasma in the mild group was 71.46(45.86-86.33)pg/m L,but 87.24(44.63-207.26)pg/m L in the severe group.The level of norepinephrine in plasma was 148.40(119.57-172.90)pg/m L in the mild group,but 166.60(146.38-267.32)pg/m L in the severe group.As the condition worsens,the levels of adrenaline and norepinephrine in the plasma were increased,but there was no significant difference between two groups(u =-1.402,P> 0.05).Only the levels of norepinephrine in two groups have significant difference(u =-2.378,P= 0.009).(5)Comparison of the level of adrenaline and norepinephrine in the plasma of different genotypes of the HFMD patients infencted by EV71.81 cases of EV71 infected HFMD were divided into GG type with 9 cases,GC type with 34 cases and CC type with 38 cases.The levels of adrenaline in the plasma were 71.35(33.29-290.21)pg/m L,87.16(48.75-174.33)pg / m L,67.92(43.12-118.50)pg/m L,respectively.There was no significant difference between the different genotypes(H=1.686,P>0.05).The levels of norepinephrine in the plasma were 244.16(149.25-407.94)pg / m L,164.59(147.01-239.92)pg / m L and 154.74(125.11-211.98)pg / m L,respectively.There was no significant difference between the different genotypes(H=3.407,P>0.05).And in the mild group(n=22 cases)and severe group(n=59 cases)subgroup analysis,there was no significant difference between the different genotypes(P>0.05).Also there was no significant difference between the epinephrine and norepinephrine levels of different alleles(P>0.05).Conclusions:(1)With the exacerbation of HFMD,the level of norepinephrine in the blood increased and it was the early warning indicators of the severe HFMD.(2)CC was the highest in the genotype of β1-adrenergic receptor located in 1165,followed by GC,GG.The highest frequency of allele is C.(3)β1 adrenergic receptor located in 1165 gene polymorphism did not increase the risk of susceptibility and severity in the HFMD patients infencted by EV71,and it also did not affect the metabolism of adrenaline and norepinephrine levels in children.(4)Subgroup analysis of gender-based,There were no significant gender differences in the distribution of alleles and alleles in β1 adrenergic receptor located in 1165.