The Study Of ACTN3/MLCK Single-Nucleotide Polymorphism And Their Relationship With Exertional Rhabdomyolysis

Rhabdomyolysis is an acute clinical syndrome determined by serious injury of skeletal muscle. There are so many precipitating causes of rhabdomyolysis such as trauma, drug, toxin, some muscle diseases and exertion. And the focus of our research is exertional rhabdomyolysis (ERB) which occurs in association with physical exercise. It was thought that only strenuous physical trainings could lead to rhabdomyolysis. However, in our clinical work, we found that there were many patients with ERB whose physical activities were not high before they developed symptoms, and even only low-intensity sports could evoke symptoms like backache, muscle soreness, obviously increased serum creatine kinase (CK), even black urinary which are indications of rhabdomyolysis. Some individuals have the cases of repeated episodes of these problems. Both the domestic and foreign researches have shown that genetic mutations made this phenomenon. We found two genes might be related with ER through gene analysis. To make sure the relationship between the ACTN3 and MLCK genotype and ERB, we tested all their serum creatine kinase and other biochemical indices, then extracted DNA from immortalized lymphocyte cells established by blood samples of these 50 patients with ERB and 63 healthy volunteers, then detected and their ACTN3/MLCK genotype by PCR and genetic sequencing technology. The results showed that compared with Caucasian control, the allele frequencies and gene polymorphisms of ACTN/MCLK of our subjects had significant statistic differences (χ2=9.53, P=0.01 VS χ2=9.46, P=0.002, χ2=10.84, P=0.004 VS χ2=8.83, F=0.004). The allele frequency of ACTN3 in Han as follows:RR=39%, RX=46%, XX=14.3%, except the frequency of homozygous wild type (RR) in our patient group was lower than that in control group 19.5%VS 39%), other genotypes of ACTN3 in our patient group was higher than that in control group(64.5% VS 46%,16.1% VS 14.3%), and the allele frequencies and gene polymorphisms of ACTN of our subjects between patient group and control group had significant statistic difference(x2=5.06, P=0.04< 0.05, χ2=85.10,P=0.00<0.01). The allele frequency of MLCK in Han as follows:CC=55.6%,CA=43.4%, the frequency of homozygous wild type (CC) in our patient group was lower than that in control group (29%VS 55.6%), the heterozygote type (CA) in patient group was higher than that in control group(71% VS 44.4%), and the allele frequencies and gene polymorphisms of MLCK of our subjects between patient group and control group had significant statistic difference (χ2=10.84, P=0.004<0.05和χ2=8.83, P=0.004 <0.05).The basal value of serum creatine kinase of individuals with ACTN3 RX genotype was lower than values of those with XX genotype in control group and the difference was statistically significant(P=0.04). There were no statistical significances between the basal values of serum creatine kinase of people with RR genotype and RX genotype and XXgenotype in control (P>0.05). And the levels of serum creatine kinase of people with these three genotypes had no differences after sports (P>0.05).The basal value of serum creatine kinase of individuals with ACTN3 RX genotype was lower than values of those with XX genotype in patient group and the difference was statistically significant(P=0.012). There were no statistical significances between the basal values of serum creatine kinase of people with RR genotype and RX genotype and XXgenotype in control (P=0.06, P=0.4).The basal value of serum creatine kinase of individuals with MLCK CA genotype was higher than values of those with CC genotype in control group before sports and the differences were statistically significant(P=0.03). The level of serum creatine kinase of individuals with MLCK CA genotype was lower than that of those with CC genotype in patients group and the differences were statistically significant(P=0.012).There was no significant difference between value of serum creatine kinase of individuals with MLCK CA genotype and that of those with CC genotype in control group after sports (P=0.15).Conclusion:1.ACTN3 R577X had correlated with the elevated CK level, for those who have RX genotype have lower CK level than other.2. MLCK C37885A had correlated with the basic CK level.3. The individual with RX and CA genotype was less vulnerable to CK abnormal increase pose-exercise.