Association Between Methylmalonic Acid and Alpha-Klotho in American Adults:a Cross-Sectional Study

Methylmalonic acid is a surrogate biomarker of mitochondrial dysfunction and oxidative stress. Serum soluble α-Klotho, as a key anti-aging factor, is regarded as one of the biomarkers of aging .The correlation between Methylmalonic Acid (MMA) and Alpha-Klotho (α-Klotho) remains uncertain .This study aims to explore the relationship between MMA and Alpha-Klothoα-Klotho in American adults .
Based on the availability of complete biochemical assays for methylmalonic acid (MMA) and α-Klotho, we restricted our analyses to the 2011–2014 cycles of the National Health and Nutrition Examination Survey (NHANES), which included 5,216 eligible participants with comprehensive laboratory data .Due to the limited amount of data, there may be a selection bias.In this study , MMA serves as the independent variable while α-Klotho functions as the dependent variable .MMA is a categorical variable , while α-Klotho is a categorical variable .The covariates examined include sociodemographic factors , lifestyle choices , and various systemic diseases . Logistic regression was used to assess the associations between covariates and different independent groups .To explore the relationship between serum MMA levels and α-Klotho , we employed three models : Model 1 adjusted for age , gender , race/ethnicity , education , Marital status ,Poverty Income Ratio (PIR) ,smoking, Body Mass Index (BMI)and Physical activity (PA) .Model 2 included all variables from Model 1 plus Cardiovascular diseases (CVD),Hypertension, Diabetes Mellitus (DM) .Considering the collinearity problem ,Model 3 adjusted for Marital status ,PIR ,Educations ,Smoke ,PA ,CVD ,Hypertension , DM ,Glycated Hemoglobin A1c (HbA1c) , High-Density Lipoprotein (HDL) ,Vitamin B12 (VitB12) , Glomerular Filtration Rate (eGFR).

甲基丙二酸（Methylmalonic acid，MMA）是线粒体功能障碍与氧化应激的替代生物标志物。血清可溶性α-Klotho作为关键抗衰老因子，被视为衰老相关生物标志物之一。目前甲基丙二酸（MMA）与α-Klotho之间的关联尚不明确。本研究旨在探讨美国成年人血清MMA与α-Klotho的相关性。
基于甲基丙二酸（MMA）与α-Klotho完整生化检测数据的可获得性，本研究将分析范围限定于2011-2014年周期的美国国家健康与营养检查调查（National Health and Nutrition Examination Survey，NHANES），共纳入5216名具备完整实验室检测数据的合格受试者。由于数据量有限，本研究可能存在选择偏倚。
本研究中，MMA作为自变量，α-Klotho作为因变量，二者均为分类变量。所纳入的协变量包括社会人口学因素、生活方式选择及各类系统性疾病。采用Logistic回归分析评估协变量与不同自变量分组间的关联。
为探讨血清MMA水平与α-Klotho的相关性，本研究构建了3种回归模型：模型1校正年龄、性别、种族/族裔、教育水平、婚姻状况、贫困收入比（Poverty Income Ratio，PIR）、吸烟状态、体质量指数（Body Mass Index，BMI）及体力活动（Physical activity，PA）；模型2在模型1的基础上，额外纳入心血管疾病（Cardiovascular diseases，CVD）、高血压、糖尿病（Diabetes Mellitus，DM）；考虑到共线性问题，模型3校正婚姻状况、PIR、教育水平、吸烟状态、PA、CVD、高血压、DM、糖化血红蛋白A1c（Glycated Hemoglobin A1c，HbA1c）、高密度脂蛋白（High-Density Lipoprotein，HDL）、维生素B12（Vitamin B12，VitB12）及估算肾小球滤过率（estimated Glomerular Filtration Rate，eGFR）。