2型糖尿病家系瘦素基因启动子C2549A多态性研究

目的　了解中国人瘦素基因启动子的基因型分布 ,探讨瘦素基因多态性与血浆瘦素水平之间的关系 ,探讨瘦素基因多态性与 2型糖尿病患者及其非糖尿病一级亲属代谢间的关系。方法　以 2型糖尿病家系中的糖尿病患者、非糖尿病一级亲属为研究对象 ,应用聚合酶链反应及限制性片段长度多态性方法 ,对 489例中国人 (包括 2 69例 2型糖尿病患者、1 35例非糖尿病一级亲属和 85例正常对照 )的瘦素基因启动子 2 549位核苷酸变异 (C2 549A)进行研究 ,同时进行血浆瘦素水平、人体测量学、代谢、临床参数的检测。结果　 (1 ) 2型糖尿病患者AA基因型频率 (0 .0 63)和A等位基因频率 (0 .349)高于正常对照(AA基因型频率为 0 .0 1 2 ,A等位基因频率为 0 .2 53 ,P <0 .0 5)。 (2 )糖尿病患者中AA、AC基因型携带者空腹血浆瘦素较CC型降低 (P <0 .0 5) ,女性中AA基因型携带者空腹血浆胰岛素、胰岛素抵抗指数水平低于CC、AC基因型携带者 (P <0 .0 5) ,男性中AA、AC基因型的糖尿病病程较长 (P <0 .0 5)。 (3)非糖尿病一级亲属中女性AA基因型携带者空腹瘦素水平低于AC基因型携带者。男性AA基因型和AC基因型的空腹血浆胰岛素、胰岛素抵抗指数较CC基因型降低 (P <0 .0 5)。结论　 (1 ) 2型糖尿病患者瘦素基因C2 549A多态性与空腹血浆

C2549A polymorphism of promoter of the leptin gene in pedigrees of type 2 diabetes mellitus

Objective To ev al uate the genotype distribution of the promoter of leptin gene in Chinese populat ion, and to verify its association with the plasma leptin level and anthropometr ic, metabolic and clinical parameters in type 2 diabetic patients and their non -diabetic first degree relatives. Methods Two hundred and sixty-nine patients with diabetes and 135 non-diabetic first degre e relatives in pedigrees of type 2 diabetes mellitus, and 85 normal controls wer e screened for presence of the polymorphism by PCR-RFLP assay, and body mass in dex (BMI), fasting plasma leptin, insulin, and glucose were measured and HOMA-I R determined. Results (1) In type 2 diabetes gr oup, AA genotype frequency (0.063) and A allele frequency (0.349) were higher th an those in normal controls (0.012 and 0.253, respectively). (2) Diabetic patien ts with AA or AC genotypes showed lower fasting leptin than those with CC genoty pe (P<0.05), female carriers with AA genotype showed lower fasting insulin and lower HOMA-IR as compared with those with AC or CC genotype (P<0.05), and the male patients with AA or AC genotype had longer duration of disease than that with CC genotype. (3) In non-diabetic rel atives group, female individuals with AA genotype showed lower fasting leptin th an those with AC genotype (P<0.05). The fasting insulin and HOMA-IR of male carriers of AA or AC genotype were lower than those of CC geno type (P<0.05). Conclusion The C2549A polymorphism in leptin gene is associated with fasting leptin in pati ents with type 2 diabetes. The genotype distribution in diabetic members from di abetic pedigrees is different from that in normal controls. The A allele frequen cy in diabetic patients is higher than that in normal controls. The metabolism p henotypes defined by genotypes are different in the family members.