| [Background]Sudden sensorineural hearing loss(SSNHL)is a frequent disease in otorhinolaryngology and seriously endangering the people’s health.According to recent World Health Organization data,moderate-to-profound hearing loss affects over 360 million people worldwide,A 5-yeax follow-up study suggested that SSNHL increases the risk of stroke,and this study also noted that SSNHL patients should undergo comprehensive hematologic and neurological examination to help clinicians identify those potentially at risk for the development of stroke in the near future.Nevertheless,the etiology of sudden hearing loss is still unknown.Recently,some reports have suggested a role for nutritional status in vascular damage.Elevated serum homocysteine(Hey)and low folate levels are emerging risk factors independently associated with an increased risk of vascular damage,as are coronary artery disease,cerebral vascular disease and peripheral vascular disease.Therefore,maintaining adequate blood flowto the cochlea is critical to cochlear function and any reduction in blood supply will have a corresponding reduction in cochlear function.The results from animal models suggested that folic acid improves inner ear vascularization in hyperhomocysteinemic mice.Folate is involved in the one-carbon metabolism as essential for DNA methylation,synthesis and repair during cell regeneration.Several key enzymes,including methylenetetrahydrofolate reductase(MTHFR),MTR,and methionine synthase reductase(MTRR),are involved in the folic acid metabolic pathway.MTHFR catalyzes the reduction of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate,which participates in the remethylation of Hcy to methionine.MTR is a vitamin B 12-dependent enzyme that is essential for the remethylation of Hcy to methionine,while MTRR helps the regeneration of inactive MTR via the reductive methylation of cobalamin.Previous studie demonstrated that the MTHFR C677T polymorphism is associated with a decreased risk of Meniere’s disease.However,none of the genes that have been proposed to be involved in SSNHL risk have been accepted widely because there are populations specific.In this study,we investigated levels of Hcy,folic acid、vitamin B12 and Hey in subjects with SSNHL to determine whether folic acid deficiency induces SSNHL through mechanisms involving methylenetetrahydrofolate reductase genetic polymorphisms.[Materials and Mathods]From November 2013 to June 2015,120 consecutive patients who were the Han nationality in Yunnan region with SSNHL and visited the department of Otorhinolaryngology of the first prople’s hospital of Yunnan province were prospectively enrolled.The controls used in this study were derived from inpatients with normal listening comprehension.They were selected randomly from registrations in the department of Otorhinolaryngology of the first prople’s hospital of Yunnan province and were stratified according to age and sex.Overall,all participants four polymorphisms of the MTHFR C677T,A1298C,MTR A2756G和MTRR A66G,were investigated.Genomic DNA was extracted from peripheral blood lymphocytes using a standard procedure,and polymerase chain reaction(PCR)amplifi cation was performed.Blood samples for biochemical analysis were obtained from all subjects after overnight fasting.Levels of folic acid and vitamin B12 were determined by an ELECSYS-170 autoanalyzer using commercial kits.Hey levels were measured with a Shimadzu HPLC analyzer using Recipe commercial kits.Statistical analyses were performed using the Solutions Statistical Package for the Social Sciences(SPSS)version 19.0.For the univariate analysis of continuous variables,the t test was used to assess differences between two groups,and one-way ANOVA was used to compare two groups.Comparisons of categorical variables were performed using the chi-square test.The chi-square test was also conducted to assess the independence of the genotypic distributions of the four polymorphisms in the baseline data.Genotypes were coded as follows:wild-type homozygotes:AA for MTR and MTRR5 CC for MTHFR C677T,and AA for MTHFR A1298C;heterozygotes:AG for MTR and MTRR,CT for MTHFR C677T,and AC for MTHFR A1298C;and mutant homozygotes:GG for MTRR and TT for MTHFR C677T.A subset of 113 patients was used for a subgroup analysis in which blood folate and Hey levels were included as variables in the statistical model because blood folate and Hcy levels were measured during the first wave of examinations.The comparison of serum folate and plasma total Hcy levels according to MTHFR and MTR genotype was conducted using a general linear model.For multivariate analysis,multiple logistic regressions were performed to obtain odds ratios(ORs)for the risk of SSNHL.All values are expressed as the mean±standard deviation unless otherwise specified.A null-hypothesis probability of<0.05 was regarded as statistically significant.[Result]1、A significant difference in serum vitamin B12 was observed between the SSNHL patients and the controls.(p=0.031).Especially,the levels of vitamin B12 of extremely severe hearing loss group(including total deafness,61 cases,51.26%)have significant differences compared with other hearing loss groups(p=0.008).In contrast,there were no differences in plasma total Hey values or serum folate values between the SSNHL patients and the controls.2、The significant differences between the MTRR AA(control:28%,petients:48.67%),AG(control:60.67%,petients:38.05%)and GG(control:11.33,petients:13.27%)genotypes were significant(p<0.01).The frequency of the A allele of the MTRR polymorphism in the SSNHL patients(67.70%)was higher than that in the controls(58.33%)(p=0.028).3、Vitamin B12 levels were notably higher in the patients with the MTR AA(594.672 ± 402.70 vs.529.69±251.32 pg/ml,p=0.003),MTR AG(613.30±370.51 vs.462.32 ± 142.42 pg/ml,p=0.004),MTRR AG(668.91 ± 466.03 vs.523.34 ±210.08 pg/ml,p=0.000),MTHFR 677CC(587.61 ± 390.10 vs.497.20 ± 239.65 pg/ml,p=0.003)and MTHFR 677CT genotypes(654.10±453.07 vs.553.12±246.24 pg/ml,p=0.005).In addition,folate levels were moderately higher in the patients with the MTR AG(8,17 ± 4.86 vs.7.52 ± 3.27 pg/ml,p=0.047)and MTHFR 677CT genotypes(8.38 ± 4.57 vs.7.45 ± 3.01 pg/ml,p=0.006).4、MTHFR C677T、A1298C,MTR A2756G and MTRR A66G gene polymorphisms were not significantly associated with the risk of SSNHL.And significant results for the MTHFR A1298C polymorphism were not achieved with either model,so these data were excluded.[Conclution]1、There is statistical significance differences of the serum vitamin B12 is higher in extremely severely hearing loss group(including total deafness)of the SSNHL patients who were the han nationality in Yunnan region than that of the other hearing loss groups(p＝0.008).We speculate that extremely severe hearing loss(including total deafness)may be related to sharing a common cause of stroke,that is the inner ear blood vessel embolism or thrombosis.With high vitamin B12 levels may be one of the inner ear the expression of vascular embolization or thrombosis.2、As expected,the frequency of the A allele of the MTRR polymorphism in the SSNHL patients was higher than that in the controls.Therefore,A allele may be a pathogenic gene.3、Vitamin B12 levels were notably higher in the patients with the MTR AA,MTR AG,MTRR AG,MTHFR 677CC and MTHFR 677CT genotypes.In addition,folate levels were moderately higher in the patients with the MTR AG and MTHFR 677CT genotypes.Elevation of serum vitamin B12 and folate were not found in all subjects carrying genetic defects,suggesting that the phenotypic expression of these changes may be influenced by additional genetic polymorphisms or by the coexistence of genetic and acquired predisposing conditions.However,further prospective studies are essential to confirm the observed results.4、MTHFR C677T,A1298C,MTR A2756G 和 MTRR A66G gene polymorphisms were not significantly associated with the risk of SSNHL.objective: to observe relational changes of plasma homocysteine(Hey)and folic acid in patients with sudden total frequency deafness and to explore its clinical significance.Methods: 54 patients suffered from sudden total frequency deafness(pure tone audiometry showed increased hearing threshold at total frequency with mean auditory threshold of 0.25,0.5,1,2,4 kHz was beyond 81 dB HL),aged from18 to 69 years old.While 45 subjects without sudden sensorineural hearing loss(SSHL)matched with the case group for sex and age were collected as the control group.Blood samples for biochemical analysis were obtained from all subjects after overnight fasting.Levels of serum folic acid were determined by an ELECSYS-170 autoanalyzer using commercial kits.Hey levels were measured with a Shimadzu HPLC analyzer using Recipe commercial kits.All the patients received the same treatment strategy of Shuxuening injection,Steroid administration and hyperbaric oxygen therapy.Statistical analyses were performed using the Solutions Statistical Package for the Social Sciences(SPSS)version 19.0.For the univariate analysis of continuous variables,the t test was used to assess differences between two groups,Comparisons of treatments were performed using the chi-square test.Result: the level of plasma tHcy in patients with sudden total frequency deafness(14.77 + 6.45) umol/L is significantly higher than control group(12.59 + 2.77)umol/L,P < 0.05.Cases of group serum folic acid(7.40 + 4.03)nmol/l5 significantly lower than the control group(9.24 + 3.58)nmol/l? P < 0.05.Conclusions: elevated plasma tHcy levels and serum folic acid closely are associated in patients with sudden total frequency deafiiess.It is not satisfactory for the treatment effect of the patients with sudden total frequency deafiiess but the determination of plasma tHcy > serum folic acid may provide referential value for its treatment and prognosis evaluation. |
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