Analysis of MIR27A (rs11671784) Variant Association with Systemic Lupus Erythematous
Zenat Ahmed Khired1, Shahad W Kattan2, Ahmad Khuzaim Alzahrani3
1Department of Surgery, College of Medicine, Jazan University, Jazan 45142, Saudi Arabia.
Abstract:
Multiple microRNAs (miRs) are associated with systemic autoimmune disease susceptibility/phenotype, including systemic lupus erythematosus (SLE). With this work, we aimed to unravel the association of the miR-27a gene (MIR27A) rs11671784G/A variant with SLE risk/severity. One-hundred sixty-three adult patients with SLE and matched controls were included. A TaqMan allelic discrimination assay was applied for MIR27A genotyping. Logistic regression models were run to test the association with SLE susceptibility/risk. Genotyping of 326 participants revealed that the heterozygote form was the most common genotype among the study cohort, accounting for 72% of the population (n = 234), while A/A and G/G represented 15% (n = 49) and 13% (n = 43), respectively. Similarly, the most prevalent genotype among cases was the A/G genotype, which was present in approximately 93.3% of cases (n = 152). In contrast, only eight and three patients had A/A and G/G genotypes, respectively. The MIR27A rs11671784 variant conferred protection against the development of SLE in several genetic models, including heterozygous (G/A vs. A/A; OR = 0.10, 95% CI = 0.05-0.23), dominant (G/A + G/G vs. AA; OR = 0.15, 95% CI = 0.07-0.34), and overdominant (G/A vs. A/A + G/G; OR = 0.07, 95% CI = 0.04-0.14) models. However, the G/G genotype was associated with increased SLE risk in the recessive model (G/G vs. A/A+ G/G; OR = 17.34, 95% CI = 5.24-57.38). Furthermore, the variant showed significant associations with musculoskeletal and mucocutaneous manifestations in the patient cohort (p = 0.035 and 0.009, respectively) and platelet and white blood cell counts (p = 0.034 and 0.049, respectively). In conclusion, the MIR27A rs11671784 variant showed a potentially significant association with SLE susceptibility/risk in the studied population. Larger-scale studies on multiethnic populations are recommended to verify the results.
Insights
The MIR27A rs11671784 variant may influence systemic lupus erythematosus (SLE) risk, showing protective effects in heterozygous forms but increased risk with the G/G genotype. This genetic factor is also linked to specific SLE manifestations and blood cell counts.
Area of Science:
- Genetics
- Immunology
- Molecular Biology
Background:
- MicroRNAs (miRs) play a role in autoimmune diseases like systemic lupus erythematosus (SLE).
- The miR-27a gene (MIR27A) and its variants are implicated in disease susceptibility and phenotype.
- Understanding genetic associations is crucial for unraveling SLE pathogenesis.
Purpose of the Study:
- To investigate the association between the MIR27A rs11671784G/A variant and the risk and severity of SLE.
- To determine the genotype frequencies in SLE patients and healthy controls.
- To explore correlations between the variant and clinical manifestations or laboratory findings in SLE patients.
Main Methods:
- Genotyping of 163 adult SLE patients and matched controls using a TaqMan allelic discrimination assay for the MIR27A rs11671784 variant.
- Logistic regression models were employed to analyze the association with SLE susceptibility and risk.
- Statistical analysis was performed to assess correlations with clinical features and blood cell counts.
Main Results:
- The heterozygote genotype (G/A) was the most common in the study cohort (72%).
- The MIR27A rs11671784 variant demonstrated a protective effect against SLE development in heterozygous, dominant, and overdominant models.
- Conversely, the G/G genotype was linked to increased SLE risk in the recessive model (OR = 17.34).
- The variant was significantly associated with musculoskeletal and mucocutaneous manifestations (p=0.035, p=0.009) and altered platelet and white blood cell counts (p=0.034, p=0.049).
Conclusions:
- The MIR27A rs11671784 variant shows a significant association with SLE susceptibility and risk in the studied population.
- The G/G genotype appears to confer higher risk, while heterozygous forms may be protective.
- Further large-scale, multiethnic studies are recommended to validate these findings and their clinical implications.
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