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.

高循环同型半胱氨酸是胱硫醚β-合酶缺乏症（也称为同型半胱氨酸尿症）的主要生化特征，总血浆水平通常超过100 μ M（正常总血浆水平不超过100 μ M）。从这种疾病中发生的一系列病理学可以清楚地看出，严重的高同型半胱氨酸血症对结缔组织具有显著的有害影响-最常见的与眼睛相关的病理学变化是晶状体异位，随后是老花眼和严重近视。我们提出假设，轻度至中度高同型半胱氨酸血症是老视的危险因素。我们将把测量的代谢幅度与血浆中总同型半胱氨酸（tHcy）水平（预期负相关）以及已知与tHcy升高相关的主要遗传多态性（5，10-亚甲基四氢叶酸还原酶（MTHFR），C677 T，Ala > VaI）的分布相关联。我们期望在低振幅的个体中发现更普遍的异常遗传性状。因此，在这个试点项目中，我们提出了三个具体的目标，旨在提供初步的数据支持R 01的应用。具体目标1.招募至少30名年龄在20 - 39岁的MTHFR基因型（纯合正常、杂合、纯合突变）受试者，并测量其一只眼睛的屈光幅度。具体目标二：对于尚未获得以下数据的受试者，a）测定同型半胱氨酸（tHcy）、叶酸和维生素B12的总血浆水平; B）确定受试者关于MTHFR不耐热变体的基因型;并将DNA和血浆样本保存在-70 ℃下，以供将来扩展这些研究。具体目标3。 统计分析舒张幅度与tHcy的相关结果。MTHFR基因型和血液叶酸和维生素B12水平;使用线性回归模型进行多变量分析，以评估tHcy对调节幅度的影响，同时调整年龄，MTHFR状态，叶酸和维生素B12水平。回归系数估计值和显著性检验将基于t检验和F检验统计量。