葡萄糖激酶基因多态性与中国人非胰岛素依赖型糖尿病相关性研究

THE RELATIONSHIP BETWEEN GLUCOKINASE GENE POLYMORPHISMAND NON-INSULIN-DEPENDENT DIABETES MELLITUS IN CHINESE

目的：探讨葡萄糖激酶基因与中国北方汉族人非胰岛素依赖型糖尿病（ＮＩＤＤＭ）的关系。方法：以葡萄糖激酶基因３’端微卫星多态性为遗传标志，用多聚酶链反应（ＰＣＲ），检测各等位基因在１４５例非糖尿病对照组和１０５例ＮＩＤＤＭ病人组中的分布频率的差异。结果：共发现３个等位基因（大小为１９５ｂｐ、１９７ｂｐ、１９９ｂｐ，分别命名为Ａ，Ｂ，Ｃ）和６种基因型（ＡＡ，ＢＢ，ＣＣ，ＡＢ，ＡＣ，ＢＣ）。等位基因Ａ、Ｂ、Ｃ在非糖尿病组的频率分别为５３．４％、２５．２％和２１．４％；在ＮＩＤＤＭ组中分别为６０．０％、１７．１％、２２．９％。基因型ＡＡ、ＢＢ、ＣＣ、ＡＢ、ＡＣ、ＢＣ在非糖尿病对照组为２８．３％、６．２％、２．１％、２４．８％、２５．５％、１３．１％；在ＮＩＤＤＭ组为３６．２％、１．９％、３．８％、２０．０％、２７．６％、１０．５％。糖尿病组中Ｂ等位基因频率明显低于非糖尿病对照组（１７．１％ｖｓ２５．２％，Ｐ＝０．０３），两组的各基因型频率差异无显著性。带有Ｂ等位基因（Ｂ＋）的ＮＩＤＤＭ患者与不带有此等位基因患者（Ｂ－）的体重指数（ＢＭＩ）差异无显著性，而Ｂ－的ＮＩＤＤＭ患者诊断年龄比Ｂ＋者小（５１岁ｖｓ５６岁，Ｐ＝０?

Objective: To evaluate the relationship between glucokinase(GCK)gene and non-insulin-dependent diabetes mellitus(NIDDM) in Chinese. Methods:Utilizing the microsatellite polymorphism of GCK gene3' as a genetic marker,we detected the differences of frequences of alleles at this locus between patients with NIDDM and normal control subjects by polymerase chain reaction(PCR). Results:In the population studied, three alleles were found, which were named alleles A, B, and C, and whose sizes were 195 bp, 197 bp, and 199 bp, respectively; six genotypes(AA,BB,CC,AB,AC, and BC) were found. The frequences of alleles A, B, and C were 53.4%, 25.2%, and 21.4% in control group, and 60.0%, 17.1%, and 22.9% in NIDDM group, respectively. The frequency of genotypes AA, BB, CC, AB, AC, and BC were 28.3%, 6.2 %, 2.1%, 24.8%, 25.5% , and 13.1% in normal control group,and 36.2 %, 1.9%, 3.8%, 20.0%, 27.6% and 10.5% in NIDDM group, respectively. In addition, the differences of frequency of other alleles and each genotype between NIDDM and normal control group were not detected. The NIDDM group had a lower B allels distribution frequency compared with normal control group(17.1% vs 25.2%,P=0.03). The NIDDM patients without B allele (B-) had similar bodymass indexes(BMI) and the numbers of patients with family history of NIDDM to the NIDDM patients with B allele (B+). Patients of Bgroup were diagnosed as NIDDM at earlier age (51 vs 56 years old,P<0.05) compared with the patients of B+ group. Conclusion:There is a positive association of GCK gene or nearby gene with NIDDM in Chinese,and the allele B may be a protective factor for NIDDM in Chinese.