| BackgroundSarcopenia increases with age,which leads to a relatively higher prevalence in the elderly population.The pathogenesis has not been quite clear while genetic predisposition proved to be one of the important effectors.Previous studies have mainly focused on the potential relationship between candidate gene polymorphisms and its phenotypes.Actually,a number of risk genes have been explored.However,polymorphism studies are limited.Moreover,due to the disease complexity,the difference of genetic background and limited sample size,the current results are not completely consistent.Moreover,the replication studies from different ethnic groups with a larger sample population are quite lacking.In addition,studies in the Chinese population are relatively restricted,with the data from the general population in particular.Aims1.To describe the distribution characteristics of genotypes and alleles of the candidate genes related to muscle strength in postmenopausal women in Beijing.2.To explore the correlation between candidate gene polymorphisms and muscle strength in postmenopausal women.3.To investigate the association between the muscle strength changes and the polymorphisms of the above genes during the two-year follow up after intervention with enhanced exercise(Tai Chi movement)or vitamin D preparation.Subjects and MethodsThis research relied on the "National Key Technology R&D Program"-the Elderly Osteoporosis Fracture Prevention and Intervention Study,and eventually 598 postmenopausal women from Dongcheng district in Beijing were included,averaging(62.9±7.0)years old.The clinical data of the subjects were collected in detail and 56 SNPs of 16 genes were genotyped through the Agena Mass Array platform.The subjects were then divided into different subgroups according to their genotypes while the chair rising test and grip strength of both hands were measured and compared between subgroups.Among them,163 cases were trained with Tai Chi movement with 30 min per time and at least 3 to 5 times per week(Enhanced exercise group).A total of 271 participants were administered with elemental calcium 600mg/d combined with cholecalciferol 800IU/d or calcitriol 0.25 ?g/d(Vitamin D intervention group).The muscle strengths of upper and lower limbs were re-measured after 1-year and 2-year intervention and then compared with the baseline levels for each genotype subgroup.Results1.Fifty-three SNPs were successfully genotyped in the participants through Agena MassArray platform,and the detection rate of each SNP was more than 93%.There are other 6 SNPs that do not meet the Hardy-Weinberg balance,and then a total of 47 SNPs were included in the final statistical analysis.2.In this population included:(1)Multiple linear regression revealed that the chair rising test of subjects with AA genotype at rs540874 of ACTN3 gene was significantly longer than those with GA/GG genotype(?=2.639,95%CI=[0.632,4.646],P=0.010).Subjects with AA genotype in the METTL21C gene rs660207 were significantly increased in left grip strength compared with AG/GG genotype(?=1.278,95%CI=[0.161,2.394],P=0.025).In addition,participants genotyped with AA at PTK2 gene rs7460 site showed significantly higher right grip strengths than those with AT/TT genotype(?=0.117,95%CI=[0.019,0.210],P=0.019).(2)Comparison between groups showed that right grip strength of women with GG genotype of rs2228570 or TT genotype of rs11574143 in VDR gene was significantly higher(P=0.013,0.034).Subjects with GG genotype at rs11227532 site or CC genotype at rs3814736 site in ACTN3 gene was significantly weaker than those with other genotypes in left grip strength(P=0.008,0.004).CC homozygotes at rs2390760 of METTL21C gene were significantly lower in right grip strength compared to GC/GG genotype(P=0.034).Moreover,those with AA genotype in GR gene had longer chair rising test time(P=0.035)and lower right grip strength(P=0.035)compared with AG/GG genotype.3.During the two-year follow-up:(1)Compared with control group,the improvement of muscle strength in lower limb and left hand was more significant in subjects with AA genotype of VDR gene rs2228570 site after vitamin D intervention.However,changes of muscle strength were similar to those in the control group in other genotypes.(2)Subjects genotyped with AA at rs540874 loci on ACTN3 gene were found to improve more evidently in lower limb muscle strength when compared with control group after enhanced exercise and vitamin D intervention,while those with GG or GA genotype had similar changes to control group.(3)After intervention with vitamin D,participants with GG genotype at METTL21C gene rs660207 loci and TT genotype at PTK2 gene rs7460 loci improved more significantly in muscle strength,while changes of muscle strength were similar to the control group in other genotypes.ConclusionThis study is the first one to preliminary investigate the association between muscle strength and related gene polymorphisms in a larger sample of Chinese postmenopausal women in Dongcheng district in Beijing.Rs540874 at ACTN3 gene,rs660207 at METTL21C gene and rs7460 loci of PTK2 gene were found to be significantly associated with muscle strength through the elucidation of multiple linear regression,indicating that genetic factors may partly explain the differences in muscle strength in the study population.In addition,enhanced exercise and vitamin D intervention both can effectively improve muscle strength in subjects with AA genotype at rs540874.Muscle strength were found to improve more significantly in subjects with AA genotype at rs2228570,GG genotype at rs660207 and TT genotype at rs7460 after vitamin D intervention.Therefore,it is suggested that enhanced exercise and vitamin D intervention can effectively improve the muscle strength of postmenopausal women,and the changes of muscle force after intervention may also be related to genetic factors.Our study provides data from the Chinese population to further understand the role of genetic factors in the pathogenesis of sarcopenia.However,relevant researches are limited,and further verification and exploration of functional mechanisms are still needed in different ethnic groups at different regions. |
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