广西非常见缺失型alpha-地中海贫血分子流行病学调查

Thalassemia is one of the most important public health problems in Guangxi province. Although the government has implemented “Guangxi Thalassemia Prevention and Control Plan” early in 2010, which has lowered the birth rate of Thalassemia Major and Thalassemia Middle, the current total morbidity of the two is as high as 0.2% and the gene carrying rate of Thalassemia is as high as 21%. This leads to the conclusion that the screening method currently used is inefficient. The primary cause of this result is the inherent defect of the screening method: it is incapable of finding out static Alpha-Thalassemia and Beta-Thalassemia minor, and unable to detect the non-common gene type of Thalassemia. The non-common deletional gene mutation of Alpha-Thalassemia , which has been reported repeatedly in Guangxi province , is thought to be the possible cause for the high morbidity and high gene carrying rate of Thalassemia. However, the spectrum and the gene frequency of the non-common deletional gene mutation of Alpha-Thalassemia in Guangxi province is still ambiguous. This project seeks to build a high sensitive and high throughput screening method based on the changes of gene copy number, and to investigate the spectrum of gene mutation types and the gene frequency of the common and non-common deletional gene mutation of Alpha-Thalassemia in the 14 cities of Guangxi province, by using the new screening method, gap-PCR, and MLPA gradually. This will uncovers the relationship between non-common deletional gene mutation of Alpha-Thalassemia and the high morbidity , high gene carry rate of Thalassemia in Guangxi province, and further, to provide theoretical support for the government to improve the Mediterranean anemia prevention and control strategy.

地中海贫血是广西最重要的公共卫生问题之一。2010年政府推行“广西地贫防治计划”，使中、重型地中海贫血婴儿的出生率明显下降，但当前广西地中海贫血总发病率仍然高达0.2%，基因携带率仍然高达21%，说明目前使用的地中海贫血筛查方法存在不足。造成这个结果的主要原因是目前使用的筛查方法不能检出静止型alpha-地中海贫血和轻型beta-地中海贫血，不能检出非常见的地中海贫血。非常见的缺失型alpha-地贫基因突变在广西多有报道，这些非常见的缺失型alpha-地贫基因突变被认为是广西地贫高发病率和高携带率的可能原因。然而，其基因突变谱和基因突变频率仍未知，为揭示这个问题，我们拟建立并使用基于alpha-珠蛋白基因拷贝数变化的高通量高灵敏筛查方法，联合使用gap-PCR和MLPA，调查常见的和非常见的缺失型alpha-地贫的基因突变谱和基因突变频率，为政府调整地中海贫血防控策略提供理论支撑.

地中海贫血是广西最重要的公共卫生问题之一。2010年起，广西自治区政府推行“地中海贫血防治计划”，使中、重型地中海贫血婴儿的出生率明显下降，但当前地中海贫血的总发病率仍然高达0.2%，地中海贫血基因携带率仍然高达21%，可能原因是现行使用的地中海贫血筛查方法不能检出静止型或非常见的地中海贫血。本课题拟开展“广西非常见缺失型alpha-地中海贫血分子流行病学调查”研究，通过研制检测试剂，探索检测方法，调查广西非常见缺失型alpha-地中海贫血存在的可能性、基因突变谱，以及基因突变频率等，以便分析其对现行防治策略的影响，为当地政府修订地贫防治策略提供科学依据。目前，课题取得了以下成果：. （1）建立了基于α-珠蛋白基因拷贝数相对定量技术的缺失型α-地中海贫血的检测方法-三重TaqMan实时荧光定量PCR检测技术。. （2）利用建立的技术完成了广西百色地区1568例人群标本地贫基因检测，检出缺失型α-地中海贫血452例，检出率28.83%。其中，常见缺失型444例，占比98.23%；泰国缺失型7例，占比1.55%；非常见缺失型1例，占比0.22%。泰国缺失型中，--Thai/αα 4例，占比0.88%；--Thai /-α3.7 2例，占比0.44%；--Thai/-α4.2 1例，占比0.22%。. （3）调查广西地区1至10岁儿童人群缺失型α-地贫和其他类型地贫基因型分布情况。研究发现：71,459例样本中，11,821人检出有地贫。其中，7,615人为α-地贫，占比64.42%；3,507人为β-地贫，占比29.67%；699人为α复合β-地贫，占比5.91%。其中，- -SEA 为主要缺失突变，占54.23%；- -SEA /αα为主要突变基因。. （4）研究中发现、鉴定出5种非常见缺失型α-地贫基因突变类型。其中，--SEA/占比30.63%，-α3.7/占比18.27%，α4.2/占比5.25%，—Thai 占比0.77%，-α-21.9占比0.11%。. 课题建立的三重TaqMan实时荧光定量PCR检测技术，填补了现有检测技术的不足，减少了罕见地中海贫血的漏诊。

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