Association Between Sarcopenia And Genetic Polymorphism Of ACTN3,ACE,CNTF,IGF-1 In Tibetans

ObjectiveThe purpose of this study is to analyze the genetic polymorphism in sarcopenia and healthy people,which include the SNP R577 X in ACTN3 gene,the SNP G1357 A in CNTF gene,the I/D polymorphism in ACE gene and the STR CA in IGF-1 gene.MethodsEighty-six patients were enrolled in the sarcopenia group(male: n=43,female: n=43),and 86 healthy adults were enrolled in the control group(male: n=44,female: n=42),172 in total.The target DNA fragment of the SNP R577 X in ACTN3 gene,the SNP G1357 A in CNTF gene,the I/D polymorphism in ACE gene and the STR CA in IGF-1 gene were amplified by PCR.The genetic polymorphisms were analyzed by Sanger sequencing,ABI genetic analyzer and agarose gel electrophoresis.One-way analysis of variance was used to analyze the association of gene polymorphism with body morphology and body composition indicators.Chi-square test was used to analyze the distribution characteristics of gene polymorphisms in the dystrophic group and healthy group.The relationship between gene-gene interaction and sarcopenia was analyzed buy using GMDR software.Logistic regression analysis was used to verify the gene-gene model.Results1.The frequencies of the SNP R577 X in ACTN3 gene each genotype in sarcopenia group were: RR:34.9%;RX:45.3%;XX:19.8%.The frequencies of ACTN3 each genotype in control group were: RR:29.0%;RX:47.7;XX:23.3%.The data of healthy control group was consistent with Hardy-weinber’s law and could represent the population.in the female group,there were differences in height(P = 0.01)and grip strength(P =0.04)between the three genotypes.There was no significantly difference between the sarcopenia group and the controls.2.The frequencies of the SNP G1357 A in CNTF gene for each genotype in sarcopenia group were: GG:79.1%;GA:20.9%;AA:0%.The frequencies of ACTN3 for each genotype in control group were: GG:73.8%;GA:19.0%;AA:7.1%.The data of healthy control group was consistent with Hardy-weinber’s law and could represent the population.There was no statistical difference between the three genotypes and each body shape and body composition index.The frequencies of the CNTF GG genotype(P =0.00)and G allele(P =0.00)were significantly higher in sarcopenia group than those-of controls.After gender stratification,the frequencies of the CNTF GG genotype(P =0.03)and G allele(P =0.02)were significantly higher in male sarcopenia group than those in male controls.The frequencies of the CNTF G allele(P =0.05)were significantly higher in female sarcopenia group than those in female controls.3.The frequencies of the I/D polymorphism in ACE gene for each genotype in sarcopenia group were: II:39.5%;ID:38.4%;DD:22.1%.The frequencies of ACE for each genotype in control group were: II:48.8%;ID:45.4%;DD:5.8%.The data of healthy control group was consistent with Hardy-weinber’s law and could representat the population.There were differences in body weight(P = 0.05)and BMI(P = 0.00)between the three genotypes in the male group.The frequencies of the ACE DD genotype(P =0.01)and D allele(P =0.01)were significantly higher in sarcopenia group those in controls.After gender stratification,the frequencies of the ACE D allele(P =0.02)were significantly higher in male sarcopenia group than those in male controls.4.The frequencies of the STR CA in IGF-1 gene for each genotype in sarcopenia group were: 19/19:9.3%;19/-:8.1%;-/-:82.6%.The frequencies of IGF-1 for each genotype in control group were: 19/19:2.3%;19/-:12.8%;-/-:84.9%.The data of healthy control group was consistent with Hardy-weinber’s law and could represent the population.There were differences in grip strength(P = 0.04),lean body mass(P = 0.02),body muscle mass(P = 0.02),and trunk muscle mass(P = 0.02)among the three genotypes in the male group.There were differences in height(P =0.01)and grip strength(P =0.00)between the three genotypes in the female group.There was no significantly difference between the sarcopenia group and the controls.After gender stratification,the frequencies of the IGF-1 19 allele(P =0.00)were significantly higher in male sarcopenia group than those in male controls.After gender stratification,the frequencies of the IGF-1 19/19 genotype(P =0.01)and 19 allele(P =0.02)were significantly higher in male sarcopenia group than those in male controls.5.There were interactions of polymorphisms in sarcopenia among the SNP R577 X in ACTN3 gene,the SNP G1357 A in CNTF gene,the I/D polymorphism in ACE gene and the STR CA in IGF-1 gene.Genotype model ACTN3 R577X—CNTF G1357A—IGF-1(CA)n—ACE I/D model:(CT)—(GG)—(-/-)—(ID)carriers have a reduced risk of sarcopenia,0.25 times that of other genotype carriers(P =0.02).Conclusions1.The SNP G1357 A in CNTF gene,the I/D polymorphism in ACE and the STR CA in IGF-1 gene can be used as molecular genetic markers of Tibetan in Tibetan sarcopenia.2.The interaction between the SNP R577 X in ACTN3 gene,the SNP G1357 A in CNTF gene,the I/D polymorphism in ACE gene and the STR CA in IGF-1 gene is associated with decreased risk of sarcopenia.