磷酸二酯酶单核苷酸多态性与双相障碍的关联分析

发布时间：2018-05-07 16:19

本文选题：双相障碍 + 磷酸二酯酶　；参考：《郑州大学》2014年硕士论文

【摘要】：目的探讨磷酸二酯酶单核苷酸多态性与双相障碍的关系，寻找与双相障碍有关的生物遗传学标志。方法 1.依据国际疾病与相关健康问题统计分类第十版（ICD-10）关于双相障碍的诊断标准，共纳入汉族患者432例（以下简称病例组），其中男性182例，女性250例；在相应的地区范围内选择569名汉族健康对照（以下简称对照组），其中男性322名，女性247名；分别比较病例组和对照组的基因型、等位基因频率的分布差异，分析其与双相障碍的关联意义。 2.采用荧光实时定量PCR技术，检测PDE4A rs1051738、rs7256672的SNPs。 3.采用SPSS17.0for windows软件包进行数据的统计与分析。采用拟合优度卡方检验，分析样本基因型、等位基因频率是否符合Hardy-Weinderg（H-W）平衡定律；采用χ2检验对病例组、对照组的基因型和等位基因频率进行比较；显著性水平为p=0.05。结果 1.两组PDE4A SNPs的H-W检验对两组汉族人群DNA样本的rs1051738、rs7256672的2个SNPs位点的检测，408个患者样本、569个健康对照样本完成了rs1051738的检测；432个患者样本、481个健康对照样本完成了rs7256672的检测。经H-W检验，，2个位点均符合Hardy-Weinderg平衡定律（p0.05）。 2.病例组与对照组PDE4ASNPs基因型和等位基因频率比较 2.1病例组与对照组PDE4A rs1051738的基因型和等位基因频率比较发现：病例组rs1051738的AA、AC和CC三种基因型频率分别为0.12、0.08和0.80，对照组为0.02、0.19和0.79，两组基因型频率比较发现，病例组CC型明显高于对照组，差异有显著性意义(χ2=58.962，df=1，p0.001)；病例组A等位基因频率为0.16，C等位基因频率为0.84，对照组A等位基因频率为0.12，C等位基因频率为0.88，两组等位基因频率比较后发现，病例组C等位基因频率明显高于对照组，差异具有统计学意义(χ2=8.319，df=1，p=0.004)。 2.2病例组与对照组PDE4A rs7256672的基因型和等位基因频率比较发现：病例组rs7256672的GG、GT和TT三种基因型频率分别为0.18、0.50和0.32，对照组为0.20、0.48和0.32，两组基因型频率比较，差异无显著性意义（χ2=0.956，df=1，p=0.620）；病例组G等位基因频率为0.43，T等位基因频率为0.57，对照组G等位基因频率为0.45，T等位基因频率为0.55，两组等位基因频率比较，差异无显著性意义(χ2=0.580，df=1，p=0.446)。 3.男、女患者的2个SNPs基因型和等位基因频率比较 3.1男、女患者的rs1051738基因型和等位基因频率比较发现：男性患者组的AA、AC和CC三种基因型频率分别为0.12、0.09和0.79，女性患者组为0.13、0.07和0.80，两组基因型频率比较未发现差异有显著性意义(χ2=0.388，df=1，p=0.824)；男性患者组A等位基因频率为0.17，C等位基因频率为0.83，女性患者组A等位基因频率为0.16，C等位基因频率为0.84，两组等位基因频率比较未发现差异有显著性意义(χ2=0.050，df=1，p=0.823)。 3.2男、女患者的rs7256672基因型和等位基因频率比较发现：男性患者组的GG、GT和TT三种基因型频率分别为0.18、0.53和0.29，女性患者组为0.18、0.48和0.34，两组基因型频率比较未发现差异有显著性意义（χ2=1.970，df=1，p=0.373）；男性患者组G等位基因频率为0.45，T等位基因频率为0.55，女性患者组G等位基因频率为0.41，T等位基因频率为0.59，两组等位基因频率比较未发现差异有显著性意义(χ2=0.983，df=1，p=0.321)。 4.病例组与对照组中男性的2个SNPs基因型和等位基因频率比较两组男性的rs1051738的基因型频率比较发现差异具有显著性意义(χ2=35.777，df=1，p0.001)，两组等位基因频率比较未发现差异有显著性意义(χ2=3.235，df=1，p=0.072)。两组男性的rs7256672的基因型及等位基因频率比较均未发现差异有显著性意义(p0.05)。 5.病例组与对照组中女性的2个SNPs基因型和等位基因频率比较两组女性的rs1051738的基因型和等位基因频率比较均具有显著性意义(p 0.05)；而rs7256672在女性病例组与对照组间比较，其基因型和等位基因频率比较均未发现差异具有显著性意义(p0.05)。结论 1.在中国汉族人群中，PDE4A的rs1051738与双相障碍存在关联，可能是具有标志性意义的功能位点。 2.在中国汉族人群中，没有发现PDE4A的rs7256672与双相障碍存在关联的证据，可能不是有标志性意义的位点。
[Abstract]:objective
Objective to explore the relationship between phosphodiesterase single nucleotide polymorphism and bipolar disorder, and to search for biologic markers related to bipolar disorder.
Method
1. according to the tenth edition of the international statistical classification of diseases and related health problems (ICD-10), 432 cases of Han patients (hereinafter referred to as case group) were included, including 182 males and 250 females, and 569 Han healthy controls (hereinafter referred to as the control group) were selected in the corresponding area, including 322 men and 247 women. The difference of genotype frequencies and allele frequencies between case group and control group was analyzed, and their correlation with bipolar disorder was analyzed.
2. fluorescence real-time quantitative PCR was used to detect PDE4A rs1051738 and rs7256672 SNPs..
3. use the SPSS17.0for windows software package to carry out the statistics and analysis of the data. Use the goodness of fit chi square test to analyze whether the genotype and allele frequency conform to the Hardy-Weinderg (H-W) equilibrium law; the genotype and allele frequency of the control group are compared with the x 2 test, and the significant level is p=0.05.
Result
1. two groups of PDE4A SNPs H-W tests were tested for rs1051738, rs7256672, 2 SNPs loci in two groups of Han population, 408 patient samples, 569 healthy control samples to complete rs1051738 detection; 432 patient samples, 481 healthy control samples completed rs7256672 detection. Through H-W, 2 sites were consistent with Hardy-Weinderg. The law of equilibrium (P0.05).
2. comparison of PDE4ASNPs genotype and allele frequency between case group and control group
2.1 case group and the control group PDE4A rs1051738 genotype and allele frequency comparison found that the case group rs1051738 AA, AC and CC three genotypes were 0.12,0.08 and 0.80, the control group was 0.02,0.19 and 0.79, the two groups of genotype frequency comparison found that the case group CC significantly higher than the control group, the difference was significant (x 2=58.962). Df=1, p0.001); the frequency of A allele in the case group was 0.16, the frequency of C allele was 0.84, the frequency of A allele in the control group was 0.12, the frequency of C allele was 0.88. The frequency of the two alleles of the two groups was found to be significantly higher than that of the control group, and the difference was statistically significant (x 2=8.319, df=1, p=0.004).
In 2.2 case group and the control group, the genotype and allele frequency of PDE4A rs7256672 showed that the frequency of GG, GT and TT in the case group was 0.18,0.50 and 0.32, the control group was 0.20,0.48 and 0.32. The difference of genotype frequencies of the two groups was not significant (x 2=0.956, df=1, p=0.620), and the frequency of the allele frequency of the case group was equal to the allele frequency. The rate was 0.43, the frequency of T allele was 0.57, the frequency of G allele in the control group was 0.45, the frequency of T allele was 0.55, and the difference of allele frequencies of the two groups was not significant (x 2=0.580, df=1, p=0.446).
Comparison of 2 SNPs genotype and allele frequencies between 3. male and female patients
The rs1051738 genotype and allele frequency of 3.1 male and female patients showed that the three genotypes of AA, AC and CC in male patients were 0.12,0.09 and 0.79 respectively, and the female patients were 0.13,0.07 and 0.80. The genotype frequencies of the two groups were not significantly different (x 2=0.388, df=1, p=0.824), and the A allele in male patients. The frequency was 0.17, the frequency of C allele was 0.83, the frequency of A allele was 0.16 and the frequency of C allele was 0.84 in female patients, and there was no significant difference in the frequency of two alleles (x 2=0.050, df=1, p=0.823).
The rs7256672 genotype and allele frequency of 3.2 male and female patients showed that the three genotypes of GG, GT and TT in male patients were 0.18,0.53 and 0.29 respectively, and the female patients were 0.18,0.48 and 0.34. The genotype frequencies of the two groups were not significantly different (x 2=1.970, df=1, p=0.373), and the G allele in male patients. The frequency was 0.45, the frequency of T allele was 0.55, the frequency of G allele was 0.41 and the frequency of T allele was 0.59 in female patients, and there was no significant difference in the frequency of two alleles (x 2=0.983, df=1, p=0.321).
Comparison of 2 SNPs genotype and allele frequencies between 4. case group and control group
The genotypic frequency of rs1051738 in two groups of men showed significant difference (x 2=35.777, df=1, p0.001), and there was no significant difference in the frequency of the two groups of alleles (x 2=3.235, df=1, p=0.072).
There was no significant difference in the genotype and allele frequencies of rs7256672 between the two groups (P0.05).
Comparison of 2 SNPs genotype and allele frequencies between 5. case group and control group
The genotype and allele frequency of rs1051738 in the two groups of women were both significant (P 0.05), while rs7256672 in the female case group and the control group had no significant difference in genotype and allele frequency (P0.05).
conclusion
1. in Chinese Han population, PDE4A rs1051738 is associated with bipolar disorder, and may be a marker functional site.
2. in Chinese Han population, there is no evidence that PDE4A rs7256672 is associated with bipolar disorder. It may not be a landmark locus.

【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R741

【参考文献】