# Exploring the role of gonadotropins in Down syndrome

> **NIH NIH R21** · UNIVERSITY OF NORTH TEXAS HLTH SCI CTR · 2020 · $403,584

## Abstract

PROJECT SUMMARY/ABSTRACT
Down syndrome (DS) is a common chromosomal disorder that results from the triplication of
chromosome 21. Comorbid medical conditions frequently occur among individuals with DS;
however, opthalamic disorders such as keratoconus occurs 6 times more often among this
population as compared to the general population. Keratoconus is a known multifactorial,
progressive, degenerative disease of the cornea; however, the etiology of the disease remains
unclear. Our recent work has found that hormone-regulated Prolactin-Induced Protein (PIP) is a
potential biomarker of keratoconus but the link between DS and keratoconus remains unclear.
Pathway analysis has further linked comorbid DS and keratoconus through gonadotropins and
serum amyloid A1 (SAA), a protein linked in a series of studies to cognitive dysfunction among
adults with DS. The proposed study aims to determine and validate the role of gonadotropins in
the DS population with the keratoconus co-morbidity with the long-term goal to better
understand the underlying mechanisms that result in increased risk for ocular co-morbidities
such as keratoconus among this population. This pilot study will include n=90 participants (n=30
DS; n=30 comorbid DS and Keratoconus; n=30 healthy controls). All participants will provide
biofluid samples of tears and plasma, which will be assayed on an electrochemiluminescence
(ECL) platform. Analyses will be performed using R and SPSS 24 (IBM) in a series of steps.
Support Vector Machine (SVM) analyses will be applied to examine the use of biomarkers to
detect disease presence (i.e. keratoconus comorbidity). Least absolute shrinkage and selection
operator (LASSO) analyses will help with variable selection in order to enhance the prediction
accuracy of the models. Biomarkers will include hormone specific (LSH, LH, GNRH, LHR,
FSHR, GNRHR) as well as a panel of plasma proteins including biomarkers of inflammation
linked with cognitive dysfunction (SAA, CRP, ICAM1, VCAM1, IL-6, IL-10, TNF-α, IL-5, IL-7,
Eotaxin-3, TARC, A2M, B2M, FVII, TNC, Adiponectin, FABP-3, IL-18, PPY, TPO and I-309).
Diagnosis of keratoconus will be utilized as the dependent variable. If successful, data obtained
from this study could help facility the development of a screening tool for detecting individuals
with DS who are at risk for development of keratoconus, with the goal of defining potential
enrollment into clinical trials.

## Key facts

- **NIH application ID:** 10108508
- **Project number:** 1R21EY032320-01
- **Recipient organization:** UNIVERSITY OF NORTH TEXAS HLTH SCI CTR
- **Principal Investigator:** Dimitrios Karamichos
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $403,584
- **Award type:** 1
- **Project period:** 2020-09-30 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10108508

## Citation

> US National Institutes of Health, RePORTER application 10108508, Exploring the role of gonadotropins in Down syndrome (1R21EY032320-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10108508. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*