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<p>Psoriasis is a multifactorial skin disease where genetics plays a significant role in predisposition and therapeutic drug response. Several genetic loci associated with disease risk have been reported in ethnically diverse populations; however, a comprehensive and rigorous analysis is lacking. Furthermore, pharmacogenomic variants associated with psoriasis may explain variability in therapeutic response; nevertheless, evidence from ethnically diverse populations remains inadequate. Therefore, this study aimed to determine the genetic association with psoriasis susceptibility or protection through meta-analysis, to explore pharmacogenomic variants linked to therapeutic response, and assess the prevalence of these variants in South Asian populations. We systematically searched PubMed and Google Scholar for original studies on the genetic association with psoriasis. Two reviewers extracted the data using the inclusion criteria: case-control studies of type-I/type-II psoriasis patients with allelic/genotyping data of a locus showing a significant OR in ≥ 3 independent studies. Exclusion criteria employed were case series/familial reports only, meta-analysis/reviews, conference abstracts, comorbidities, missing genetic/statistical data, and animal model studies. Meta-analysis of 103 eligible studies was conducted using the Mantel-Haenszel method employing either a fixed or random-effects model based on data heterogeneity. Pharmacogenomic variants data regarding drug response in psoriasis treatment were retrieved from the PharmGKB database. The allele frequencies of these variants were obtained from the 1000-Genomes database. Our meta-analysis revealed a significant association of 18 SNPs with the risk of psoriasis predisposition. A highly significant association was found with MHC (rs10484554; <i>p</i> &lt; 0.01) and TNIP (rs17728338; <i>p</i> &lt; 0.01) variants with the susceptibility to psoriasis. Variant IL-12B rs6887695 is shown to have a protective role (<i>p</i> &lt; 0.01), though its allele frequencies are varied substantially across ethnic groups, emphasizing ethnic heterogeneity. We also identified 40 Pharmacogenomic variants in 32 genes associated with psoriatic drug efficacy or toxicity, with variable allele frequencies worldwide. Notably, 12 pharmacogenomics variants exhibited allele frequencies ≥ 0.5 in South Asians, with implications for therapeutic outcomes in this population. This comprehensive study highlights the genetic variants associated with susceptibility or protection against psoriasis and identifies pharmacogenomic variants influencing drug response. It also signifies the importance of population-specific pharmacogenomic studies of anti-psoriatic therapies, especially in underrepresented populations like South Asians. The knowledge of disease/population-specific psoriasis-associated genetic variants and pharmacogenomic data provides fundamentals for personalized treatment strategies for psoriasis patients.</p>

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Genetic predisposition to psoriasis and therapeutic drug response. A meta-analysis

  • 期刊论文

  • 发表日期：

    2026年7月25日

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  • Ali Raza,
  • Abdul Rafay Khan,
  • Khizar Ali,
  • Sayed Hajan Shah,
  • Sadaf Firasat,
  • Erum Hanif,
  • Pashp Mala,
  • Humaira Talat,
  • Shagufta Khaliq,
  • Aiysha Abid

摘要

Psoriasis is a multifactorial skin disease where genetics plays a significant role in predisposition and therapeutic drug response. Several genetic loci associated with disease risk have been reported in ethnically diverse populations; however, a comprehensive and rigorous analysis is lacking. Furthermore, pharmacogenomic variants associated with psoriasis may explain variability in therapeutic response; nevertheless, evidence from ethnically diverse populations remains inadequate. Therefore, this study aimed to determine the genetic association with psoriasis susceptibility or protection through meta-analysis, to explore pharmacogenomic variants linked to therapeutic response, and assess the prevalence of these variants in South Asian populations. We systematically searched PubMed and Google Scholar for original studies on the genetic association with psoriasis. Two reviewers extracted the data using the inclusion criteria: case-control studies of type-I/type-II psoriasis patients with allelic/genotyping data of a locus showing a significant OR in ≥ 3 independent studies. Exclusion criteria employed were case series/familial reports only, meta-analysis/reviews, conference abstracts, comorbidities, missing genetic/statistical data, and animal model studies. Meta-analysis of 103 eligible studies was conducted using the Mantel-Haenszel method employing either a fixed or random-effects model based on data heterogeneity. Pharmacogenomic variants data regarding drug response in psoriasis treatment were retrieved from the PharmGKB database. The allele frequencies of these variants were obtained from the 1000-Genomes database. Our meta-analysis revealed a significant association of 18 SNPs with the risk of psoriasis predisposition. A highly significant association was found with MHC (rs10484554; p < 0.01) and TNIP (rs17728338; p < 0.01) variants with the susceptibility to psoriasis. Variant IL-12B rs6887695 is shown to have a protective role (p < 0.01), though its allele frequencies are varied substantially across ethnic groups, emphasizing ethnic heterogeneity. We also identified 40 Pharmacogenomic variants in 32 genes associated with psoriatic drug efficacy or toxicity, with variable allele frequencies worldwide. Notably, 12 pharmacogenomics variants exhibited allele frequencies ≥ 0.5 in South Asians, with implications for therapeutic outcomes in this population. This comprehensive study highlights the genetic variants associated with susceptibility or protection against psoriasis and identifies pharmacogenomic variants influencing drug response. It also signifies the importance of population-specific pharmacogenomic studies of anti-psoriatic therapies, especially in underrepresented populations like South Asians. The knowledge of disease/population-specific psoriasis-associated genetic variants and pharmacogenomic data provides fundamentals for personalized treatment strategies for psoriasis patients.