PPARγ2基因Pro12Ala多态性与维吾尔族2型糖尿病患者亲级关系的研究
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摘要
目的分析PPARγ2基因Pro12Ala位点多态性与新疆维吾尔族2型糖尿病家系中不同亲级的相关性。方法以新疆62个维吾尔族2型糖尿病核心家系为样本,采用PPAP(population and pedigree analysis programs)统计软件和Penrose’s法来研究其遗传方式;将75个新疆维吾尔族2型糖尿病家系一级亲和二级亲成员481人做两组比较分析,采用基因芯片SNP-Stream实验方法检测PPARGAMA位点多态性,应用SPSS13.0统计软件分析PPARγ2基因Pro12Ala基因多态性是否在2型糖尿病家系不同亲级关系存在差异。结果1)2型糖尿病家系一级亲的遗传度为0.578,二级亲的遗传度为0.032,随亲缘系数降低而减小;2)一级和二级亲属之间PPAR-γ2基因Pro12Ala基因型和等位基因频率分布均无统计学差异(P<0.05);3)空腹血糖、体质指数、血压、腹围、空腹胰岛素、胰岛素抵抗指数等参数在PPARγ2基因Pro12Ala三种不同基因型之间没有明显差异,无统计学意义;结论新疆维吾尔族2型糖尿病的遗传度随着亲缘系数的降低而减小;一级和二级亲属之间PPARγ2基因Pro12Ala基因型频率分布均无明显差异。
Objective To analyse the relationship between PPARγ2 gene Pro12Ala polymorphism and diabetes in familial type 2 diabetes mellitus of Uygur in Xinjiang. Methods We chose 62 Uygur type 2 diabetic families and apply PPAP statistic software to analyse the genetic pattern. The polymorphism of PPARγ2gene Pro12Ala measured by SNP-Stream of gene chip method. SPSS13.0 statistic analysis software was used to test the relationship between PPAR-γ2 gene Pro12Ala polymorphism and the first and second degree relative in familial type 2 diabetes mellitus. Results 1)The heritability of the first degree relative in Uygur familial type 2 diabetes was 0.578 and of the second degree relative was 0.032. With the down of the degree relative, the heritability was decreased; 2)There was no significant difference in PPARγ2gene Pro12Ala polymorphism between the first and second degree relative in familial type 2 diabetes mellitus; 3)The all data including BMI、FPG、Lipid and et al) had no significant difference among three kinds of genotypes. Conclusion With the down of the degree relative, the heritability was decreased ; There was no significant difference in PPARγ2 gene Pro12Ala polymorphism between the first and second degree relative in familial type 2 diabetes mellitus.
Objective To analyse the relationship between PPARγ2 gene Pro12Ala polymorphism and diabetes in familial type 2 diabetes mellitus of Uygur in Xinjiang. Methods We chose 62 Uygur type 2 diabetic families and apply PPAP statistic software to analyse the genetic pattern. The polymorphism of PPARγ2gene Pro12Ala measured by SNP-Stream of gene chip method. SPSS13.0 statistic analysis software was used to test the relationship between PPAR-γ2 gene Pro12Ala polymorphism and the first and second degree relative in familial type 2 diabetes mellitus. Results 1)The heritability of the first degree relative in Uygur familial type 2 diabetes was 0.578 and of the second degree relative was 0.032. With the down of the degree relative, the heritability was decreased; 2)There was no significant difference in PPARγ2gene Pro12Ala polymorphism between the first and second degree relative in familial type 2 diabetes mellitus; 3)The all data including BMI、FPG、Lipid and et al) had no significant difference among three kinds of genotypes. Conclusion With the down of the degree relative, the heritability was decreased ; There was no significant difference in PPARγ2 gene Pro12Ala polymorphism between the first and second degree relative in familial type 2 diabetes mellitus.
引文
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[11] Rocchi S, Auwerx J. PPARγ: a versatile metabolic regulator[ J ]. AnnMed, 1999, 31 (5) : 342--351.
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[14] Deeb S S, Fajas L, Nemoto M, et al. A Prol2Ala substitution in PPARγ2 associated with decreased recep tor activity. 1ower bodymass index and impaired insulin sensitivity[ J ]. Nat Genet, 1998, 20: 284 -287.
[15] Altshuler D, et al. The common PPARγPro12Ala polymorphisms is associated with decreased risk of type 2 diabetes [ J ]. Nat Genet, 2000, 26 (1) : 76 - 80.
[16] Meirhaeghe A, Amouyel P. Impact of genetic variation of PPARγ[ J ]. Mol GenetMetab, 2004, 83 (1 - 2) : 93 - 102.
[17] MoonMK, Cho YM, Jung HS, et al. Genetic polymorphisms in peroxisome proliferator - activated recep tor gamma are associated with type 2 diabetes mellitus and obesity in the Korean population[ J ]. D iabetM ed, 2005; 22 ( 9) : 1161 -1166.
[18] Doney AS, Fischer B, Cecil JE, et al. Association of the Pro12Ala and C1431T variants of PPARγand their haplotypes with susceptibility to Type 2 diabetes[ J ]. D iabetolo2gia, 2004; 47 (3) : 555– 558.
[19] Andrulionyte L, Peltola P, Jean - Louis, et al. Single nucleotide polymorphisms of PPARD in combination with the Gly482Ser substitution of PGC - 1A and the ro12Ala substitution of PPARγ2 p redict the conversion from impaired glucose tolerance to type 2 diabetes the STOP - N IDDM Trial[ J ]. D iabetes, 2006; 55: 2148– 2152.
[20] Stefanski A, Majkowska L, Ciechanowicz A, et al. Lack of association between the Pro12Ala polymorphism in PPAR- gamma gene and body weight changes, insulin resistance and chronic diabetic comp lications in obese patients with type 2 diabetes[ J ]. A rch M ed Res, 2006; 37 (6) : 736- 743.
[21]博健,池上博司,李远栋,等.过氧化物酶体增殖物激活受体γ2基因Pro12 Ala可能是我国汉族人2型糖尿病的保护性等位基因.中国糖尿病杂志, 2005, 13(5): 363-365.
[22] LL Li, XL Ma, JX Ran, et al. Genetic polymorphism of peroxisome Proliferator-activated receptor-gamma 2 Pro12Ala on ethnic susceptibility to diabetes in Uygur, Kazak and Han subjects. Clin Exp Pharmacol Physiol, Feb 2008; 35(2): 187-91.
[1] Issemann I, Green S.Activation of a member of the steroid hormone re-ceptorsuperfamily by peroxisome proliferators [J].Nature, 1990, 347(6294): 645-650
[2] Rocchi S, Auwerx J.PPARγ: a versatile metabolic regulator[J].AnnMed, 1999, 31 (5) : 342-351.
[3] Sundvold H, L ien S.Identification of a novel PPARγp romoter in man and transactivation by the nuclear recep tor RORalpha1 [J].Biochem Biophys Res Commun, 2001, 287 (2) : 383-390.
[4] Owen GI, Zelent A.Origins and evolutionary diversification of the nuclear receptor superfamily [J ].Cell Mol Life Sci, 2000, 57 (5) : 809-827.
[5] Fajas L, Fruchart JC, Auwerx J.PPARgamma3 mRNA: a distinct PPARγmRNA subtype transcribed from an independent promoter[J].FEBS Lett, 1998, 438 (122) : 55-60.
[6] Tautenhahn A, Brüne B, von Knethen A.Activation2induced PPARγexp ression sensitizes p rimary human T cells toward apop tosis[J].Leukoc Biol, 2003, 73 (5) : 665-672.
[7] Rosen ED, Hsu CH, Wang X, et al.C/EBPalpha induces adipogenesis through PPARγ: a unified pathway[ J ].Genes Dev, 2002, 16 (1) : 22-26.
[8] Zingarelli B, Cook JA.PPARγis a new therapeutic target in sepsis and inflammation[ J ].Shock, 2005, 23 (5) : 393-399.
[9] Yen C J, et al.Molecular scanning of the human peroxisome p roliferator activated recep tor gamma ( hPPAR gamma ) gene in diabetic Caucasians : identification of a Pro12Ala PPAR gamma 2 missense mutation[ J ].Biochem Biophys Res Commun, 1997, 241 ( 2) : 270~274.
[10] ZHAO Yan - Hong, CONG Xiang - Feng, CHEN Xi.Association studies of PPARγC1431T polymorphism and obesity[J].Mol Cardiol China, 2003, 3 (3) : 140~143.
[11] Mori H, et al.The Pro12→Ala substitution in PPARγis associated with resistance to development of diabetes in the general populations :possible involvement in impairment of insulin secretion in individuals with type 2 diabetes[J].Diabetes, 2001, 50 (4) : 891~894.
[12] Meirhaeghe A, Amouyel P.Impact of genetic variation of PPARγ[ J ].Mol GenetMetab, 2004, 83 (1 - 2) : 93 - 102.
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