Homocysteine's role in the causation of presbyopia

同型半胱氨酸在老花眼病因中的作用

• 批准号: 6546989
• 负责人: CHARLES W PRINCE
• 金额: $ 7.25万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-08-01 至 2005-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6546989
• 关键词: age difference; aging; blood chemistry; clinical research; cryopreservation; disease /disorder proneness /risk; eye refraction disorder; female; folate; genetic polymorphism; genetic susceptibility; genotype; homocysteine; homocystinuria; human subject; lens; miscellaneous oxidoreductase; myopia; patient oriented research; statistics /biometry; vision tests; vitamin B12; young adult human (21-34)

Elevated circulating homocysteine is the major biochemical feature of cystathionine beta-synthase deficiency (also known as homocystinuria) with total plasma levels usually exceeding 100microM (normal total plasma levels do not exceed 100microM. It is clear from the set of pathologies that occurs in this disorder that severe hyperhomocysteinemia has significant detrimental effects on connective tissues- the most commonly observed pathological changes related to the eye are ectopia lentis preceded by presbyopia and severe myopia. We propose the hypothesis that mild to moderate hyperhomocysteinemia is a risk factor for presbyopia. We shall correlate measured accommodative amplitude with total Hcy (tHcy) levels in plasma (an inverse correlation is expected), and with the distribution of a major genetic polymorphism (5,10-methylenetera-hydrofolate reductase (MTHFR), C677T, Ala > VaI) known to be associated with elevated tHcy. We expect to find the abnormal genetic trait more prevalent among individuals with low accommodative amplitude. In this Pilot Project, we therefore propose three specific aims designed to provide preliminary data supportive of an R01 application. Specific Aim 1. To recruit at least 30 subjects of each MTHFR genotype (homozygous normal, heterozygote, homozygous mutant), aged 20 to 39 years, and measure their accommodative amplitude in one eye. Specific Aim 2: For subjects for whom the following data are not already available, to: a) determine total plasma levels of homocysteine (tHcy), folate and vitamin B12; b) establish the genotype of the participants with regard to the thermolabile variant of MTHFR; and c0 archive of -70 degrees Centigrade the DNA and plasma samples for future extension of these studies. Specific Aim 3. To statistically analyze the results correlating accommodative amplitude to tHcy. MTHFR genotype and blood folate and vitamin B12 levels; to undertake multivariate analysis using the linear regression model to assess the effect of tHcy on accommodation amplitude while adjusting for age, MTHFR status, folate, and vitamin B12 levels. Estimates of regression coefficients and tests of significance will be based on t-test and F-test statistics.

循环循环升高是半胱氨酸β-合酶缺乏症（也称为型囊性尿素）的主要生物化学特征，总血浆水平通常超过100microm（正常总血浆水平（正常总血浆水平）（不超过100microm，都超过100microm。显然，大多数病理学在这种严重的组织中，严重的超级疾病造成了严重的疾病，这是严重的超级疾病的疾病。通常观察到与眼睛有关的病理学变化是在长期的和严重的近视的前提。 （5,10-甲基苯基氢叶酸还原酶（MTHFR），C677T，ALA> vai）已知与THCY升高有关。因此，在这个试点项目中，我们提出了三个特定的目标，旨在提供R01应用程序的初步数据。具体目的1。要招募每种MTHFR基因型的至少30名受试者（纯合法线，杂合子，纯合突变体），年龄在20至39岁之间，并一只眼睛测量其可容纳振幅。特定目的2：对于尚未获得以下数据的受试者，to：a）确定同型半胱氨酸（THCY），叶酸和维生素B12的总血浆水平； b）建立参与者的基因型在MTHFR的热质体变体方面； -70度的C0档案库，以将来扩展这些研究的DNA和等离子体样品。具体目的3。统计分析结果将可容纳幅度与THCY相关的结果。 MTHFR基因型和血叶酸和维生素B12水平；使用线性回归模型进行多变量分析，以评估THCY对年龄，MTHFR状态，叶酸和维生素B12水平的适应幅度的影响。回归系数和显着性测试的估计将基于t检验和F检验统计数据。