TGF-β1基因多态性与多囊卵巢综合征相关性分析

发布时间：2018-05-12 06:28

本文选题：TGF-β1 + 多囊卵巢综合征（PCOS）　；参考：《广州医科大学》2014年硕士论文

【摘要】：目的:探讨TGF-β1基因5个位点（rs4803457、rs11466313、rs2317130、rs1800469、rs1800470）的单核苷酸多态性及其构成的单体型与中国广东汉族妇女多囊卵巢综合征的相关性。方法：选择广东地区汉族妇女为本次研究对象，采用病例-对照研究分析方法，对328例多囊卵巢综合征患者和358例正常妇女进行研究。利用聚合酶链式反应和Snapshot技术对TGF-β1基因5个位点：rs4803457（C/T）、rs11466313（deletion/AGG）、rs2317130（C/T）、rs1800469（C/T）、rs1800470（C/T）进行基因分型检测，并对这5个位点进行连锁不平衡和单体型分析，分别比较不同基因型和单体型与多囊卵巢综合征发病风险之间的关系。结果： 1、中国广东地区汉族妇女中存在TGF-β1基因rs4803457、rs11466313、rs2317130、rs1800469、rs1800470多态位点。 2、TGF-β1基因rs4803457位点TT、CT、CC基因型频率在在PCOS组中的频率分别为28.05%、48.78%和23.17%，C/T等位基因频率分别为38.13%和61.87%；在对照组中的频率分布分别为36.59%、47.49%和15.92%，C/T等位基因频率分别为39.66%和60.34%，，两组间基因型频率分布与等位基因频率分布存在统计学差异（P＜0.05）。 3、建立多因素logistic回归模型分析显示，经校正年龄、BMI因素后纳入方程的为年龄、BMI和rs4803457位点CC基因型，与rs4803457位点非CC基因型相比较，CC基因型的OR值为1.75（95%CI=1.11-2.75），即具有rs4803457位点CC基因型患PCOS的风险是其他基因型的1.75倍，并且与年龄、BMI有一定的相互作用。 4、TGF-β1基因rs11466313、rs2217130、rs1800470位点的基因型频率分布及等位基因频率分布无统计学差异（P＞0.05）。rs1800469位点基因型频率分布无统计学差异，但等位基因频率分布有统计学差异（P＜0.05）。 5、研究群体TGF-β1基因5个研究位点间均存在连锁不平衡，其中，rs4803457、rs11466313、rs1800469和rs1800470之间具有强LD关系（D’＞0.8，r2＞0.8）。 6、单体型分析发现由该5个位点构成的T-CCC、C-CCC、C-CTC单体型频率在PCOS组中明显增加，与对照组相比有统计学差异（P＜0.01）。 7、建立多因素logistic回归模型分析显示，经校正年龄、体重指数（BMI）后，以野生型等位基因组成的单体型T-CTC作为对照，单体型T-CCC、C-CCC、C-CTC可能是PCOS易感性的致病性因素（OR值分别为3.20、5.65、5.74；95%CI分别为1.56-6.55、1.59-20.02、2.84-11.59）。结论： 1、TGF-β1基因SNPs rs4803457C/T、 rs1800469C/T基因多态可能与中国广东地区汉族妇女PCOS发生有关，而暂未发现rs11466313、rs2317130、rs1800470位点多态与PCOS发生有关。 2、TGF-β1基因SNP rs4803457位点CC基因型可能是PCOS的危险因素。 3、5个多态位点构成的T-CCC、C-CCC、C-CTC单体型可能是中国广东地区汉族妇女PCOS的危险因素。
[Abstract]:Objective: to investigate the single nucleotide polymorphisms of 5 loci of TGF- 尾 1 gene, rs4803457rs11466313rs2317130, rs1800469, rs1800470) and their association with polycystic ovary syndrome (PCOS) in Chinese Han women. Methods: 328 patients with polycystic ovary syndrome (PCOS) and 358 normal women were studied by case-control study. Polymerase chain reaction (PCR) and Snapshot technique were used to detect the genotyping of TGF- 尾 1 gene at 5: rs4803457C / Tr / R / R 11466313 deletions rs2317130 / C / T / Rs1800469 C / T / 1800470C / T, and to analyze the linkage imbalance and haplotype of the five loci. To compare the relationship between different genotypes and haplotypes and the risk of polycystic ovary syndrome (PCOS). Results: 1. There is a polymorphic locus of TGF- 尾 1 gene rs4803457rs11466313rs2317130rs1800469rs1800469 in Han women in Guangdong, China. (2) the frequencies of TGF- 尾 1 rs4803457 locus TTT / CTCC genotype in PCOS group were 28.05, 48.78% and 23.1717g / T, 38.13% and 61.87%, respectively, and the frequencies in the control group were 36.599.49% and 15.922% respectively, and 60.34T allele frequencies in the two groups were 39.66% and 60.34% respectively, and the frequencies of TGF- 尾 1 gene were 38.13% and 61.87% respectively in the PCOS group, and the frequencies in the control group were 39.66% and 60.34%, respectively, and the frequencies in the control group were 39.66% and 60.34%, respectively. There was statistical difference between the frequency distribution of factor and allele (P < 0.05). 3. The multivariate logistic regression model analysis showed that the age logistic and rs4803457 locus CC genotypes were included in the equation after the adjustment of age and BMI factors. Compared with non-CC genotypes of rs4803457 locus, the OR of CC genotype was 1.75 ~ (95) CI = 1.11-2.75, that is to say, CC genotype with rs4803457 locus was 1.75 times more likely to have PCOS than other genotypes, and there was some interaction between CC genotype and age. 4There was no significant difference in genotype frequency distribution and allelic frequency distribution of rs11466313nrs2217130 rs1800470 and allelic frequencies of TGF- 尾 1 gene (P > 0.05).rs1800469 locus), but there was significant difference in allelic frequency distribution (P < 0.05). 5. There was linkage disequilibrium among the five loci of TGF- 尾 1 gene in the study population. There was a strong LD relationship between rs4803457rs11466313rs1800469 and rs1800470. 6. Haplotype analysis showed that the haplotype frequency of T-CCCnC-CCCnC-CTC was significantly higher in PCOS group than that in control group (P < 0.01). 7. The multivariate logistic regression model analysis showed that after adjusting age and body mass index (BMI), using haplotype T-CTC composed of wild type alleles as control, the OR value of haplotype T-CCCfC C-CCCfC-CTC might be 3.2055.6BMI5.749595 CI was 1.56-6.555% 1.59-20.02U 2.84-11.59g, respectively. Conclusion: 1TGF- 尾 1 gene SNPs rs4803457C / T, rs1800469C/T gene polymorphism may be related to the occurrence of PCOS in Han women in Guangdong area of China, but no rs114663130rs2317130rs1800470 polymorphism has been found to be associated with the occurrence of PCOS. 2CC genotype at SNP rs4803457 site of TGF- 尾 1 gene may be a risk factor for PCOS. The haplotype of T-CCCU C-CCCnC-CTC composed of 3, 5 polymorphic loci may be a risk factor for PCOS in Han women in Guangdong area of China.
【学位授予单位】：广州医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R711.75

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