Association of GHRL and CYP19A1 Variants with Uterine Leiomyoma: An Exploratory Case–Control Study with In Silico Annotation
4 affiliations
- 1Department of Gynaecology and Obstetrics, Faculty of Medicine, Muğla Sıtkı Koçman University, 48000 Mugla, Turkey
- 2Department of Medical Biology, Health Sciences Institution, Muğla Sıtkı Koçman University, 48000 Mugla, Turkey
- 3Department of Bioinformatics, Graduate School of Natural and Applied Sciences, Mugla Sıtkı Koçman University, 48000 Mugla, Turkey
- 4Department of Medical Biology, Faculty of Medicine, Muğla Sıtkı Koçman University, 48000 Mugla, Turkey
Abstract
Uterine leiomyomas (ULMs) are common benign gynecological tumors associated with estrogen signaling and metabolic–endocrine pathways. This study investigated the associations of CYP19A1 (cytochrome P450 family 19 subfamily A member 1; rs2414096) and GHRL (ghrelin and obestatin prepropeptide; rs34911341, rs696217) polymorphisms with leiomyoma risk and evaluated their potential functional effects in silico. This case–control study included 65 women with uterine leiomyoma and 72 healthy controls. Genotyping was performed using polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP). Associations were assessed using Firth’s penalized-likelihood logistic regression under additive, dominant, and recessive models, with adjustment for age, body mass index (BMI), and parity. Functional predictions employed CADD, PolyPhen-2, SIFT, SpliceAI, and I-Mutant v2.0. Cases and controls were comparable in age, BMI, and parity (all p > 0.05). CYP19A1 rs2414096 was not associated with leiomyoma risk. Conversely, GHRL rs34911341 showed a significant association under the adjusted additive model (OR = 2.85, 95% CI: 1.59–5.45, p = 0.0003; FDR q = 0.001) and remained independently associated in the joint multivariable model (OR = 2.75, 95% CI: 1.52–5.30, p = 0.0006). GHRL rs696217 showed a nominal additive association (adjusted OR = 2.11, p = 0.037), which did not remain significant after false discovery rate (FDR) correction or in the joint model. Recessive associations for both GHRL variants were affected by complete separation. In silico analyses classified rs2414096 as benign, whereas both GHRL variants were computationally predicted to be potentially deleterious and to reduce protein stability. These findings suggest a candidate association between GHRL rs34911341 and leiomyoma susceptibility. Given the modest sample size, control-group Hardy–Weinberg equilibrium deviations, and absence of biochemical peptide measurements, larger multicenter studies are needed for validation.
Related
- Vitamin A and D Status, Selected Genetic Variants, and Allergy-Related Phenotypes: An Exploratory Retrospective Study
- Genetic variants involved in sperm motility and their association with sperm motility parameters and risk of male infertility: a systematic review and meta-analysis protocol
- Association between plasma brain-derived p-tau variants and anxiety phenotypes in older adults
- Genetic Variants, Lifestyle Factors and Changes in Body Fat Percentage in Young Adults: An Exploratory Prospective Study
- Association of EGLN1 and EGLN3 genetic variants with COVID-19 severity in a Mexican population
BibTeX
@article{akbaba2026association,
title = {{Association of GHRL and CYP19A1 Variants with Uterine Leiomyoma: An Exploratory Case–Control Study with In Silico Annotation}},
author = {Eren Akbaba and Burak Sezgin and Ayşegül Demirtaş and Çilem Özdemir and Tuba Edgünlü},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27219625},
url = {https://www.mdpi.com/1422-0067/27/21/9625},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Association of GHRL and CYP19A1 Variants with Uterine Leiomyoma: An Exploratory Case–Control Study with In Silico Annotation
AU - Eren Akbaba
AU - Burak Sezgin
AU - Ayşegül Demirtaş
AU - Çilem Özdemir
AU - Tuba Edgünlü
PY - 2026
DA - 2026/10/27
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219625
UR - https://www.mdpi.com/1422-0067/27/21/9625
AB - Uterine leiomyomas (ULMs) are common benign gynecological tumors associated with estrogen signaling and metabolic–endocrine pathways. This study investigated the associations of CYP19A1 (cytochrome P450 family 19 subfamily A member 1; rs2414096) and GHRL (ghrelin and obestatin prepropeptide; rs34911341, rs696217) polymorphisms with leiomyoma risk and evaluated their potential functional effects in silico. This case–control study included 65 women with uterine leiomyoma and 72 healthy controls. Genotyping was performed using polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP). Associations were assessed using Firth’s penalized-likelihood logistic regression under additive, dominant, and recessive models, with adjustment for age, body mass index (BMI), and parity. Functional predictions employed CADD, PolyPhen-2, SIFT, SpliceAI, and I-Mutant v2.0. Cases and controls were comparable in age, BMI, and parity (all p > 0.05). CYP19A1 rs2414096 was not associated with leiomyoma risk. Conversely, GHRL rs34911341 showed a significant association under the adjusted additive model (OR = 2.85, 95% CI: 1.59–5.45, p = 0.0003; FDR q = 0.001) and remained independently associated in the joint multivariable model (OR = 2.75, 95% CI: 1.52–5.30, p = 0.0006). GHRL rs696217 showed a nominal additive association (adjusted OR = 2.11, p = 0.037), which did not remain significant after false discovery rate (FDR) correction or in the joint model. Recessive associations for both GHRL variants were affected by complete separation. In silico analyses classified rs2414096 as benign, whereas both GHRL variants were computationally predicted to be potentially deleterious and to reduce protein stability. These findings suggest a candidate association between GHRL rs34911341 and leiomyoma susceptibility. Given the modest sample size, control-group Hardy–Weinberg equilibrium deviations, and absence of biochemical peptide measurements, larger multicenter studies are needed for validation.
SN - 1422-0067
ER -