Open Access

ARTICLE

Association between interleukin-6 promoter polymorphisms and osteoporosis in javanese postmenopausal women

Sri Lestari Utami^1,2, Mohammad Hidayat³, Diana Lyrawati⁴, Loeki Enggar Fitri^5,*

1 Doctoral Program of Medical Science, Faculty of Medicine, Universitas Brawijaya, Malang, 65145, Indonesia
2 Department of Biomedical, Medical Faculty, Universitas Wijaya Kusuma Surabaya, Surabaya, 60225, Indonesia
3 Department of Orthopaedic, Faculty of Medicine, Universitas Brawijaya, Malang, 65145, Indonesia
4 Department of Pharmacy, Faculty of Medicine, Universitas Brawijaya, Malang, 65145, Indonesia
5 Department of Clinical Parasitology, Faculty of Medicine, Universitas Brawijaya, Malang, 65145, Indonesia

* Corresponding Author: LE Fitri,

European Cytokine Network 2025, 36(4), 74-83. https://doi.org/10.1684/ecn.2025.0507

Accepted 26 January 2026;

Abstract

Background: The expression of the interleukin-6 (IL-6) gene promoter and its variations in postmenopausal women of Javanese ethnicity remains unexplored. This study aimed to examine IL-6 promoter polymorphisms at positions -174G/C, -572G/C, -597A/G, and -634C/G and their associations to osteoporosis status in Javanese postmenopausal women. Methods: A cross-sectional study was conducted at an elderly integrated service post in Sidoarjo, Indonesia. Among 699 screened individuals, 66 postmenopausal women fulfilled the inclusion and exclusion criteria. Bone mineral density was assessed using dual-energy X-ray absorptiometry (DXA), and osteoporosis status was defined based on T-score values. IL-6 promoter polymorphisms were genotyped by sequencing PCR-amplified promoter regions. IL-6 mRNA expression was assessed using RT-PCR followed by densitometric analysis, and serum IL-6 concentrations were determined using enzyme-linked immunosorbent assay. Results: Our study showed that osteoporosis and osteopenia were predominant (28.8% and 57.6%, respectively), and 13.6% of subjects had normal BMD. The IL-6 promoter variant genotypes and frequencies were as follows: at -174 GG (0.924), CC (0.045), and GC (0.030); at -572 GC (0.424), CC (0.406), and GG (0.167); at -597 GG (0.924) and GA (0.076); and at -634 CC (1). The IL-6 mRNA and protein level (median 6.06, IQR 5.0398 pg/mL) were not statistically different among individuals with different genotypes and with normal, osteopenia, or osteoporosis status. Ordinal regression showed that IL-6 promoter polymorphisms were not significantly associated with osteoporosis status. The polymorphisms of the IL-6 promoter were detected in Javanese postmenopausal women; however, such polymorphisms did not correlate with IL-6 mRNA and protein levels nor osteoporosis status. Conclusion: IL-6 promoter polymorphisms were present in Javanese postmenopausal women; however, these variants were not associated with IL-6 expression at the mRNA or protein level, nor with osteoporosis status.

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Keywords

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