摘要
目的利用单核苷酸多态性(SNP)标记熏在中国北方汉族2型糖尿病相关基因定位区域(1p36.33-p36.23、1q24.3-25.1及1q42.12-42.13)内寻找疾病易感基因位点以及与疾病相关的单倍型。方法通过公共SNP数据库和对样本库全基因测序寻找SNP位点的途径,在定位区域内选择了33个候选基因中的124个SNP位点,用测序法对236例北方汉族散发2型糖尿病患者及152例正常对照个体进行SNP基因分型及病例-对照关联分析,并对具显著性差异的SNP位点进行单倍型分析。结果124个SNP位点中有4个SNP位点的分布频率在病例组和正常对照组存在显著差异穴P<0.05雪,分别为sAC基因中的rs203849(P=0.005,OR=1.60)和rs203826(P=0.016,OR=1.60),PANK4基因中的rs7535528(P=0.028,OR=1.45)和CASP9基因中的rs884363(P=0.043,OR=1.37)。在这4个SNP位点构成的组合型中发现,有2种组合型的频率分布在病例组与对照组之间差异有显著性穴P<0.001雪。此外,对sAC基因的单倍型分析发现,有4种单倍型与疾病发生相关。结论sAC、PANK4和CASP9基因为中国北方汉族人群2型糖尿病候选易感基因,这3个基因可能在2型糖尿病易感性上有协同作用。
Objective To search for the susceptibility variant(s)of type 2 diabetes in the susceptible regions on chr.1(1p36.23-36.33, 1q24.3-25.1, and 1q42.12-42.13)by genotyping SNP markers in case-control DNA samples and identifying the haplotype associated with type 2 diabetes. Methods Totally 124 SNPs in 33 candidate genes in the mapped regions were chosen from public SNP data or identified by sequencing the samples that were used to search for SNP locus. Sequencing method was used to genotype the loci for 236 sporadic type 2 diabetes patients and 152 normal subjects in Northern Han Chinese population. The haplotypes with significant difference were further analyzed. Results Of 124 SNPs successfully typed, 4 SNPs that showed association with diabetes status were found: rs203849(P = 0.005, OR=1.60)and rs203826(P = 0.016, OR=1.60)located in sAC gene, rs7535528(P = 0.028, OR=1.45)located in PANK4, rs884363(P = 0.043, OR=1.37)located in CASP9 gene. In addition, the frequencies of two combination types from these 4 SNP genotypes were signifi- cantly different between case and control groups(P < 0.001). Furthermore, four haplotypes associated with diabetes were found in haplotype analysis of sAC gene. Conclusion sAC, PANK4, and CASP9 may be associated with type 2 diabetes in Han population in north China, and it seems that the synergetic effect of these genes is responsible for the development of type 2 diabetes.
出处
《中国医学科学院学报》
CAS
CSCD
北大核心
2005年第3期274-279,共6页
Acta Academiae Medicinae Sinicae
基金
科技部专项基金(2002BA711A10-02
2002BA711A05
2004CCA01400)
国家自然科学基金(30170441
30370668)
北京市自然科学基金(7032033)~~
关键词
2型糖尿病
单核苷酸多态性
单倍型
易感基因
type 2 diabetes
single nucleotide polymorphism
haplotypes
susceptibility gene
