Homocysteine's role in the causation of presbyopia

循环同型半胱氨酸升高是半胱硫氨酸-合成酶缺乏症（也称为同型半胱氨酸尿）的主要生化特征，血浆总水平通常超过100微米（正常血浆总水平不超过100微米）。从这种疾病中发生的一系列病理可以清楚地看出，严重的高同型半胱氨酸血症对结缔组织有显著的有害影响——与眼睛有关的最常见的病理变化是异位晶状体，在老花眼和严重近视之前发生。我们提出轻度至中度高同型半胱氨酸血症是老花眼的危险因素的假设。我们将测量的调节幅度与血浆中总Hcy （tHcy）水平（预期呈负相关）以及已知与tHcy升高相关的主要遗传多态性（5,10-亚甲基-氢叶酸还原酶（MTHFR）， C677T, Ala > VaI）的分布相关联。我们期望发现异常遗传性状在调节幅度低的个体中更为普遍。因此，在这个试点项目中，我们提出了三个具体目标，旨在为R01应用程序提供初步数据支持。具体目标招募至少30名年龄在20 - 39岁的MTHFR基因型（纯合子正常、杂合子、纯合子突变）的受试者，并测量其在一只眼睛中的调节幅度。具体目标2：对于尚未获得以下数据的受试者：a)测定血浆中同型半胱氨酸（tHcy）、叶酸和维生素B12的总水平；b)确定参与者关于MTHFR热稳定性变异的基因型；并将DNA和血浆样本保存在零下70摄氏度的档案库中，以备将来扩展这些研究。具体目标3。统计分析调节幅度与tHcy的相关结果。MTHFR基因型与血叶酸和维生素B12水平；采用线性回归模型进行多变量分析，在调整年龄、MTHFR状态、叶酸和维生素B12水平的情况下，评估tHcy对调节幅度的影响。回归系数的估计和显著性检验将基于t检验和f检验统计量。

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.