Theses and Dissertations

Date of Award

5-2024

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Biochemistry and Molecular Biology

First Advisor

Robert Dearth

Second Advisor

Ravindranath Duggirala

Third Advisor

Srinivas Mummidi

Abstract

Leucine-rich alpha-2-glycoprotein 1 (LRG1) has become a major topic of research due to an increasing number of studies demonstrating its unique role in the pathogenesis of multiple human diseases including diabetes and cardiovascular disease. LRG1 has recently been identified as an adipokine, a signaling molecule secreted by adipose tissue. Furthermore, it has been correlated with intercellular signaling that promotes diet-induced hepatosteatosis and insulin resistance in mice. In this study, LRG1 serum concentrations were measured in a family-based cohort of 571 non-diabetic Mexican American children and adolescents aged 6-17 years old (mean age = 11.76 years and females = 48.2%) to determine its genetic basis (i.e., heritability [h2]) and phenotypic, genetic, and environmental correlations with various cardiometabolic risk traits (e.g., BMI, Fat Mass, Insulin, and hs-CRP). The genetic analyses were performed using the variance components analytical techniques as implemented in the computer program SOLAR. The genetic analyses were done using two types of data: Complete data set (6-17 years old individuals; N = 571; Model 1) and a subset (11-17 years old individuals; N = 313; Model 2). The heritability (additive genetic influences) analysis revealed that LRG1 is under significant and strong additive genetic influences and that heritability appears to be age-dependent (Model 1 = 42% versus Model 2 = 58%). The bivariate genetic analysis showed significant phenotypic correlations (based on Model 1 and/or 2) between LRG1 and certain phenotypes such as Fat Mass, hs-CRP, and total cholesterol. and other correlations were suggestive in nature. Significant genetic and environmental correlations were found only in the case of trait pair LRG1 and aspartate transaminase/alanine transaminase ratio (Model 2). These findings are first of their kind using data from children and adolescents, particularly Mexican Americans, and highlight the complex genetic architecture of LRG1 and its association with certain cardiometabolic traits and the potential to implement early interventions to prevent or cure complex disease conditions correlated with LRG1.

Comments

Copyright 2024 Aaron Rene Reyna.

https://go.openathens.net/redirector/utrgv.edu?url=https://www.proquest.com/pqdtglobal1/dissertations-theses/genetics-lrg1-association-with-cardiometabolic/docview/3085294160/sem-2?accountid=7119

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