β_3肾上腺能受体基因Trp64Arg变异与胰岛素抵抗的关系

ASSOCIATION OF THE Trp 64 Ar g MUTATION OF β_3-ADRENOCEPTOR GENE WITH INSULIN RESISTANCE

目的 :观察中国人群β3 肾上腺能受体 (β3 AR)基因 Trp 64Arg的变异频率 ,以及此基因变异与肥胖、胰岛素抵抗及非胰岛素依赖性糖尿病 ( NIDDM)的关系。方法 :选取互相之间无任何亲缘关系的汉族NIDDM病人 1 32例 ,年龄 ( 55.41± 1 2 .3)岁。选取无亲缘关系的汉族非 NIDDM80人 ,年龄 ( 54.1 2± 1 3.6)岁。对上述对象查体 ,查血生化指标及空腹血清 C-肽 ( C- P)。用 PCR- RFLP方法检测β3 AR基因 Trp 64Arg变异。结果 :Arg 64纯合子发生 NIDDM的相对危险性是 1 .54。Arg 64纯合子的 NIDDM病人发病年龄较早( 37.33± 6.98岁 vs.45.69± 1 1 .0 1岁 ,P<0 .0 5)。Arg64纯合子与 Trp64纯合子相比 ,前者体重指数较大( 2 8.56± 2 .58vs.2 4 .72± 5.1 2 ,P<0 .0 5) ,血 TG水平较高 ( 2 .56± 1 .2 1 mmol/L vs.1 .71± 1 .31 mmol/L,P<0 .0 5) ,血 HDL- C水平较低 ( 1 .0 1± 0 .2 3mmol/L vs.1 .32± 0 .44mmol/L,P<0 .0 5) ,空腹血 C- P水平较高 ( 1 .0 5± 0 .34pmol/L vs.0 .77± 0 .2 3pmol/L,P<0 .0 5) ,动脉舒张压较高 ( 1 1 .30± 1 .75k Pa vs.1 0 .1 0± 1 .63k Pa,P<0 .0 5)。Trp64Arg杂合子也有以上倾向 ,但与 Trp64纯合子相比无显著性差异。结论 :β3 AR基因的 Trp64Arg变异与肥胖、胰岛素抵抗?

Objective:To inve s tigate the Trp 64 Arg mutation rate in t he gene for the β 3adrenoceptor and to p robe into the relationship between the r ate and NIDDM and obesity in Chinese.Methods:We used the polymerase chain reaction to amplify a region of th e gene for β 3 adrenoceptor encoding ami no acid residues 27 to 110 in genomic DN A extracted from leukocytes from 132 pat ients with NIDDM and 80 subjects without NIDDM.The mutation resulting in replace ment of tryptophan by arginine at positi on 64 was detected by an analysis of res triction fragment length polymorphisms w ith the use of the endonuclease BstN1,wh ich cliscriminates between the normal an d mutant sequences.Results:T here was no differece between 132 patien ts with NIDDM and the subjects without N IDDM in frequency of Arg 64 allele.There was no difference in frequency allele b etween both sexes in 132 patrents with N IDDM either.However,the patients with NI DDM who were homozygotes for the Trp 64 Arg mutation tend to have an earlier age of onset of NIDDM than normal homozygot es.The relative risk (RR) of NIDDM ocurr ance was 1 54 in the Arg/Arg genotype.Whe n the data of the two groups(NIDDM and non NI DDM)were combined each other,we discover ed that the homozygous carriers of the A rg 64 allele had a significantly higher body mass index,higher triglyceride conc entration,lower HDL cholesterol concentr ation,higher fasting C peptide concentra tion,higher diastolic blood pressure tha n homozygous carriers of the Trp 64 alle le.Some of these differences were also o bserved between haterozygous Trp 64 Arg and homozygous Trp 64 Arg genotypes. Conclusion:The Trp 64 Arg p olymorphism of the β 3 adrenoceptor gene may be a genetic predisposer to obesity ,NIDDM and insulin resistance syndrome i n Chinese.