本文選題：雙相障礙 + 磷酸二酯酶　； 參考：《鄭州大學(xué)》2014年碩士論文

【摘要】：目的 探討磷酸二酯酶單核苷酸多態(tài)性與雙相障礙的關(guān)系，尋找與雙相障礙有關(guān)的生物遺傳學(xué)標(biāo)志。 方法 1.依據(jù)國際疾病與相關(guān)健康問題統(tǒng)計(jì)分類第十版（ICD-10）關(guān)于雙相障礙的診斷標(biāo)準(zhǔn)，共納入漢族患者432例（以下簡稱病例組），其中男性182例，女性250例；在相應(yīng)的地區(qū)范圍內(nèi)選擇569名漢族健康對(duì)照（以下簡稱對(duì)照組），其中男性322名，女性247名；分別比較病例組和對(duì)照組的基因型、等位基因頻率的分布差異，分析其與雙相障礙的關(guān)聯(lián)意義。 2.采用熒光實(shí)時(shí)定量PCR技術(shù)，檢測(cè)PDE4A rs1051738、rs7256672的SNPs。 3.采用SPSS17.0for windows軟件包進(jìn)行數(shù)據(jù)的統(tǒng)計(jì)與分析。采用擬合優(yōu)度卡方檢驗(yàn)，分析樣本基因型、等位基因頻率是否符合Hardy-Weinderg（H-W）平衡定律；采用χ2檢驗(yàn)對(duì)病例組、對(duì)照組的基因型和等位基因頻率進(jìn)行比較；顯著性水平為p=0.05。 結(jié)果 1.兩組PDE4A SNPs的H-W檢驗(yàn)對(duì)兩組漢族人群DNA樣本的rs1051738、rs7256672的2個(gè)SNPs位點(diǎn)的檢測(cè)，408個(gè)患者樣本、569個(gè)健康對(duì)照樣本完成了rs1051738的檢測(cè)；432個(gè)患者樣本、481個(gè)健康對(duì)照樣本完成了rs7256672的檢測(cè)。經(jīng)H-W檢驗(yàn)，，2個(gè)位點(diǎn)均符合Hardy-Weinderg平衡定律（p0.05）。 2.病例組與對(duì)照組PDE4ASNPs基因型和等位基因頻率比較 2.1病例組與對(duì)照組PDE4A rs1051738的基因型和等位基因頻率比較發(fā)現(xiàn)：病例組rs1051738的AA、AC和CC三種基因型頻率分別為0.12、0.08和0.80，對(duì)照組為0.02、0.19和0.79，兩組基因型頻率比較發(fā)現(xiàn)，病例組CC型明顯高于對(duì)照組，差異有顯著性意義(χ2=58.962，df=1，p0.001)；病例組A等位基因頻率為0.16，C等位基因頻率為0.84，對(duì)照組A等位基因頻率為0.12，C等位基因頻率為0.88，兩組等位基因頻率比較后發(fā)現(xiàn)，病例組C等位基因頻率明顯高于對(duì)照組，差異具有統(tǒng)計(jì)學(xué)意義(χ2=8.319，df=1，p=0.004)。 2.2病例組與對(duì)照組PDE4A rs7256672的基因型和等位基因頻率比較發(fā)現(xiàn)：病例組rs7256672的GG、GT和TT三種基因型頻率分別為0.18、0.50和0.32，對(duì)照組為0.20、0.48和0.32，兩組基因型頻率比較，差異無顯著性意義（χ2=0.956，df=1，p=0.620）；病例組G等位基因頻率為0.43，T等位基因頻率為0.57，對(duì)照組G等位基因頻率為0.45，T等位基因頻率為0.55，兩組等位基因頻率比較，差異無顯著性意義(χ2=0.580，df=1，p=0.446)。 3.男、女患者的2個(gè)SNPs基因型和等位基因頻率比較 3.1男、女患者的rs1051738基因型和等位基因頻率比較發(fā)現(xiàn)：男性患者組的AA、AC和CC三種基因型頻率分別為0.12、0.09和0.79，女性患者組為0.13、0.07和0.80，兩組基因型頻率比較未發(fā)現(xiàn)差異有顯著性意義(χ2=0.388，df=1，p=0.824)；男性患者組A等位基因頻率為0.17，C等位基因頻率為0.83，女性患者組A等位基因頻率為0.16，C等位基因頻率為0.84，兩組等位基因頻率比較未發(fā)現(xiàn)差異有顯著性意義(χ2=0.050，df=1，p=0.823)。 3.2男、女患者的rs7256672基因型和等位基因頻率比較發(fā)現(xiàn)：男性患者組的GG、GT和TT三種基因型頻率分別為0.18、0.53和0.29，女性患者組為0.18、0.48和0.34，兩組基因型頻率比較未發(fā)現(xiàn)差異有顯著性意義（χ2=1.970，df=1，p=0.373）；男性患者組G等位基因頻率為0.45，T等位基因頻率為0.55，女性患者組G等位基因頻率為0.41，T等位基因頻率為0.59，兩組等位基因頻率比較未發(fā)現(xiàn)差異有顯著性意義(χ2=0.983，df=1，p=0.321)。 4.病例組與對(duì)照組中男性的2個(gè)SNPs基因型和等位基因頻率比較 兩組男性的rs1051738的基因型頻率比較發(fā)現(xiàn)差異具有顯著性意義(χ2=35.777，df=1，p0.001)，兩組等位基因頻率比較未發(fā)現(xiàn)差異有顯著性意義(χ2=3.235，df=1，p=0.072)。 兩組男性的rs7256672的基因型及等位基因頻率比較均未發(fā)現(xiàn)差異有顯著性意義(p0.05)。 5.病例組與對(duì)照組中女性的2個(gè)SNPs基因型和等位基因頻率比較 兩組女性的rs1051738的基因型和等位基因頻率比較均具有顯著性意義(p 0.05)；而rs7256672在女性病例組與對(duì)照組間比較，其基因型和等位基因頻率比較均未發(fā)現(xiàn)差異具有顯著性意義(p0.05)。 結(jié)論 1.在中國漢族人群中，PDE4A的rs1051738與雙相障礙存在關(guān)聯(lián)，可能是具有標(biāo)志性意義的功能位點(diǎn)。 2.在中國漢族人群中，沒有發(fā)現(xiàn)PDE4A的rs7256672與雙相障礙存在關(guān)聯(lián)的證據(jù)，可能不是有標(biāo)志性意義的位點(diǎn)。
[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.

【學(xué)位授予單位】：鄭州大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R741

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