Effects Of CHRNA1 Genetic Polymorphism On Neuromuscular Blockade With Rocuronium

Objective: This study focus on the effects of CHRNA1 genetic polymorphism on rocuronium muscle relaxation effect。Therefore unveils the genetic feature of muscle relaxants clinical effect in Chinese, which eventually lead to individual rational administration.Methods: Ninety-five ASAⅠorⅡlaparotomy patients of both sexs, aged 18~64 yr and BMI were from 18 to 25 were divided into three groups by their genotype. Perioperative monitoring included electrocardiogram and heartrate, invasivel mean arterial blood pressure, systolic blood pressure, diastolic arterial blood pressure, peripheral oxygen saturation, heart rate variablity, bispectral index, and PETCO2. Anesthesia was induced with fentanil and propofol.The adductor pollicis muscles myopalmus single twitch height depression was detected by TOF-Watch Skelaxin monitor.Genomic DNA was extracted by using proteinase K digestion followed by a salting out procedure. CHRNA1 polymorphisms were analyzed by PCR-restriction fragment length polymorphism analysis (RFLP) and direct Sequence Analysis.Statistical analysis was performed using SPSS11.5 software package. P<0.05 was considered significant for all statistical analyses. Group comparison was performed by means of one way analysis of variance. Numeration data comparison was performed by means of two-sided contingency tables using Chi-square test.Result: Ninety-five patients were divided into three groups by their genotype: AA group (n=82), AG group (n=9), GG group (n=4). There were no significantly difference in ages, the rate of sex, body weight index, hand skin temperature in three groups(P>0.05).CHRNA1 gene promoter region SNPs PCR product is 126 bp, digested by restriction incision enzyme BstX I at 65℃for 12 hrs. A/A genotype digested to 126bp fragment, G/G genotype digested to 101bp and 25bp fragments, and A/G genotype digested to 126bp, 101bp and 25bp fragments. CHRNA1 SNP rs16862847 genotype frequency is A/A 86.3%,A/G 9.5%,G/G 4.2%. A allelic frequency is 91.1%, G allelic frequency is 8.9%.DNA sequencing result shows that AA group CHRNA1 SNP is 65th bases A; GG group is G and AG group both are A and G.Compare with AA group, the maximum adductor pollicis muscles myopalmus single twitch height depression in AG group and GG group decreased (P<0.05). But there was no significance difference between AG group and GG group(P>0.05).Compare with A/A genotype, the maximum adductor pollicis muscles myopalmus single twitch height depression of the patients whose genotype carried G allelic(A/G+G/G) decreased (P<0.05).Conclusion: The A→G mutation of CHRNA1 rs16862847 allele deereased the effect of rocuronium. CHRNA1 rs16862847 polymorphism was one of the factors to produce individual diff- erence of muscle relaxant effect in Chinese.