Background and Aims Leptin, an adipokine with immunomodulatory properties, has been implicated in rheumatoid arthritis (RA) pathogenesis. The aim of this study was to investigate the association of leptin (LEP) gene polymorphisms (rs791620 and rs7799039) with RA susceptibility, clinical characteristics, laboratory data, and musculoskeletal ultrasound (MSUS) findings in Egyptian patients. Methods This case–control study included 101 RA patients and 101 age- and sex-matched healthy controls. Genotyping of LEP rs791620 and rs7799039 polymorphisms was performed using TaqMan SNP assays. All patients underwent clinical evaluation, laboratory testing (RF, anti-CCP, ESR, CRP), disease activity assessment (DAS28-ESR/CRP), and MSUS. Results Genotype and allele frequencies of rs791620 and rs7799039 did not differ significantly between RA patients and controls (all p > 0.05). However, within the RA cohort, the rs791620 CA genotype was associated with male sex (p ≤ 0.001) and subcutaneous nodules (p = 0.009). The rs7799039 AA genotype was associated with higher patient global assessment (p = 0.031), prolonged morning stiffness (p = 0.020), and increased frequency of joint erosions (p < 0.05). There were no significant associations with inflammatory markers or disease activity scores. Multivariable regression analysis identified CRP (p < 0.001) and RF positivity (p = 0.029) as independent predictors of higher DAS28-ESR, while LEP polymorphisms were not. Conclusions In the current cohort, no significant association was detected between LEP rs791620 or rs7799039 polymorphisms and RA susceptibility. However, these variants may influence specific phenotypic characteristics, such as subcutaneous nodules and joint erosions. Consequently, additional investigations involving larger cohorts are recommended. <Table Float="No" ID="Taba"> <tgroup cols="2"> <colspec align="left" colname="c1" colnum="1" /> <colspec align="left" colname="c2" colnum="2" /> <tbody> <row> <entry align="left" nameend="c2" namest="c1"> Highlights What is known about this research topic? • Leptin is a pro-inflammatory adipokine that involved in the pathogenesis of rheumatoid arthritis (RA) through its immunomodulatory effects on both T-cells and macrophages. • Genetic polymorphisms in the leptin (LEP) gene have been linked to various autoimmune diseases, however, their role in RA susceptibility is still largely unexplored. What this study adds and its future implications: New findings: • LEP rs791620 and rs7799039 polymorphisms were not associated with RA susceptibility. • LEP rs791620 CA genotype was correlated with male sex and subcutaneous nodules, while rs7799039 AA genotype was linked to higher patient global assessment, prolonged morning stiffness, and increased joint erosions. </entry> </row> </tbody> </tgroup> </Table>

Association of leptin gene polymorphisms (rs791620 and rs7799039) with rheumatoid arthritis susceptibility and clinical manifestations: a case–control study

期刊论文
发表日期：

2026年5月18日

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Fatma Azzahraa Hisham,
Samar Tharwat,
Dalia Kamal Nassar,
Sherehan A. Abdelsalam,
Yasmin Adel,
Mohamed M. Nahas,
Nora Mostafa,
Manal M. El-Desoky

摘要

Background and Aims

Leptin, an adipokine with immunomodulatory properties, has been implicated in rheumatoid arthritis (RA) pathogenesis. The aim of this study was to investigate the association of leptin (LEP) gene polymorphisms (rs791620 and rs7799039) with RA susceptibility, clinical characteristics, laboratory data, and musculoskeletal ultrasound (MSUS) findings in Egyptian patients.

Methods

This case–control study included 101 RA patients and 101 age- and sex-matched healthy controls. Genotyping of LEP rs791620 and rs7799039 polymorphisms was performed using TaqMan SNP assays. All patients underwent clinical evaluation, laboratory testing (RF, anti-CCP, ESR, CRP), disease activity assessment (DAS28-ESR/CRP), and MSUS.

Results

Genotype and allele frequencies of rs791620 and rs7799039 did not differ significantly between RA patients and controls (all p > 0.05). However, within the RA cohort, the rs791620 CA genotype was associated with male sex (p ≤ 0.001) and subcutaneous nodules (p = 0.009). The rs7799039 AA genotype was associated with higher patient global assessment (p = 0.031), prolonged morning stiffness (p = 0.020), and increased frequency of joint erosions (p < 0.05). There were no significant associations with inflammatory markers or disease activity scores. Multivariable regression analysis identified CRP (p < 0.001) and RF positivity (p = 0.029) as independent predictors of higher DAS28-ESR, while LEP polymorphisms were not.

Conclusions

In the current cohort, no significant association was detected between LEP rs791620 or rs7799039 polymorphisms and RA susceptibility. However, these variants may influence specific phenotypic characteristics, such as subcutaneous nodules and joint erosions. Consequently, additional investigations involving larger cohorts are recommended.

Highlights

What is known about this research topic?

• Leptin is a pro-inflammatory adipokine that involved in the pathogenesis of rheumatoid arthritis (RA) through its immunomodulatory effects on both T-cells and macrophages.

• Genetic polymorphisms in the leptin (LEP) gene have been linked to various autoimmune diseases, however, their role in RA susceptibility is still largely unexplored.

What this study adds and its future implications:

New findings:

• LEP rs791620 and rs7799039 polymorphisms were not associated with RA susceptibility.

• LEP rs791620 CA genotype was correlated with male sex and subcutaneous nodules, while rs7799039 AA genotype was linked to higher patient global assessment, prolonged morning stiffness, and increased joint erosions.