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Mutations in PGRN gene associated with the risk of psoriasis in Pakistan: a case control study



Psoriasis is a chronic, autoimmune, papulosquamous skin disorder, characterized by the formation of drop-like papules and silvery-white plaques surrounded by reddened or inflamed skin, existing predominantly on the scalp, knees and elbows. The characteristic inflammation and hyperproliferation of keratinocytes in psoriasis is regulated by progranulin (PGRN), which suppresses the expression and release of inflammatory cytokines, such as TNF-α.


In this study mutation analysis of the PGRN gene was performed by extracting the genomic DNA from blood samples of 171 diagnosed psoriasis patients and controls through standard salting-out method, followed by amplification and sequencing of the targeted region of exon 5–7 of PGRN gene.


Three single nucleotide polymorphisms, rs25646, rs850713 and a novel point mutation 805A/G were identified in the PGRN gene with significant association with the disease. The variant alleles of the polymorphisms were significantly distributed among cases and controls, and statistical analysis suggested that the mutant genotypes conferred a higher risk of psoriasis development and progression. Multi-SNP haplotype analysis indicated that the CAA (OR = 8.085, 95% CI = 5.16–12.66) and the CAG (OR = 3.204, 95% CI = 1.97–5.21) haplotypes were significantly associated with psoriasis pathogenesis.


These findings demonstrate that polymorphisms in PGRN might act as potential molecular targets for early diagnosis of psoriasis in susceptible individuals.

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Psoriasis, a chronic autoimmune inflammatory skin disorder, is one of the leading skin conditions with a global prevalence ranging from 0.09 to 11.4% [1]. The disease is generally characterized by erythematous, sharply demarcated, symmetrical papules or plaques covered with thick silvery-white scales present mainly on the knees, elbows, scalp, nails, umbilicus and the lumbar region [2,3,4,5]. Psoriasis is known to negatively impact the patient’s quality of life (QoL) and its pathogenesis is mainly influenced by genetic predisposition and environmental factors, such as physical trauma, infections, smoking and alcohol consumption [6,7,8]. While psoriatic arthritis, psychological stress, obesity and metabolic syndrome, as well as cutaneous malignancies are the comorbidities associated with severe psoriasis [4, 9].

The disease presents five distinct clinical manifestations, i.e. Psoriasis Vulgaris (commonly referred to as plaque psoriasis) which is characterized by the appearance of reddened, inflamed skin with silvery-white plaques, Guttate psoriasis exists in the form of drop-like papules, while small pustules appear on the palms and feet of Pustular psoriasis patients. Erythrodermic and Inverse are the rare forms of psoriasis characterized by skin shedding and sharply demarcated, wet plaques respectively. The severity of the disease varies among patients, and greatly depends on the extent of exposure to triggering factors.

This dis-figuring disease is known to be activated by the innate immune system that releases pro-inflammatory cytokines, eventually leading to distinct epidermal and vascular hyperplasia which is a key characteristic of lesional psoriatic skin [10,11,12]. One of the key inflammatory cytokines observed to be in elevated levels in psoriasis is tumor necrosis factor α (TNF-α) which binds to its specific receptors, TNFR1 and TNFR2, and stimulates the nuclear factor kappa B (NF-κB) signaling pathway to initiate rapid transcription of other inflammatory genes such as IL-6, IL-8, IL-1β and INF-γ, as depicted in Fig. 1 [3, 13,14,15,16].

Fig. 1
figure 1

The molecular pathway of TNF and Progranulin in immune regulation. The binding of TNFα with TNFR1/2 stimulates the phosphorylation of inhibitor of kappa B kinase (IKK), leading to the activation and translocation of NF-κB into the nucleus resulting in synthesis and subsequent release of inflammatory cytokines (IL-36, IL-1, IL-8). Three domains of progranulin bind to the TNFR1 and regulate inflammation by disrupting the TNFα/NF-κB signalling pathway [17]

A TNF antagonist, Progranulin, which also serves as a growth factor protein, inhibits the TNF-α pathway by competitively binding to TNFRs (Fig. 1) [18,19,20,21,22]. Overexpression of Progranulin (encoded by the PGRN gene, located at chromosome 17 - NC_000017.11 (44,345,302..44353106)) in the epidermal keratinocytes of psoriasis patients, and elevated serum levels in patients with lesional psoriatic skin have suggested a therapeutic role of progranulin in regulating inflammation [13, 23, 24]. Progranulin is implicated in various cellular processes which include cell growth, wound healing, cartilage development, mediating inflammation, is a well-known biomarker for different cancers, and its deficiency has been linked with various neurological diseases [24, 25].

Inhibiting the TNF-α signaling pathway by blocking its receptors has the potential to induce an anti-inflammatory response in inflammatory psoriatic skin [25,26,27,28]. Hence, this study aims to contribute to the existing knowledge of disease pathogenesis by identifying genetic markers involved in the onset and aggravation of psoriasis, and investigate the loss of function single nucleotide polymorphisms in the PGRN gene that may alter the activity of progranulin protein and modify its anti-inflammatory potential.


Subject selection and sample collection

The present study comprised of 342 subjects, including 171 psoriasis patients and 171 healthy individuals as controls. Patients diagnosed with any of the five subtypes of psoriasis were included in the study while patients diagnosed with bacterial or fungal skin infections were excluded, whereas the control group consisted of healthy individuals with no history of skin disorders. A questionnaire was employed to collect the clinical details of each patient and all subjects were recruited with a written informed consent. Ethical approval for this case-control study was taken from the Institutional Review Board (IRB) of The Karachi Institute of Biotechnology and Genetic Engineering (KIBGE), and a collaboration was established with Jinnah Post Graduate Medical Centre (JPMC). Blood samples were collected from the study subjects and stored at 4 °C in vacutainers containing the anticoagulant ACD (Acid Citrate Dextrose).

DNA extraction and quantification

Genomic DNA was extracted from peripheral blood leukocytes by following the standard salting-out protocol [29]. The quality of the extracted DNA was assessed through agarose gel electrophoresis using 0.8% agarose, while the concentration and purity of the DNA were determined through nano-drop spectrophotometer (Thermo Fisher Scientific, Waltham, MA, USA).

Primer designing and PCR amplification

The sequence of the PGRN gene (ENSG00000030582) was retrieved from the Ensemble Genome database. The exome 5–7 was selected for analysis due to a higher frequency of variants that have been linked with other diseases, as cited in the dbSNP. The relative forward and reverse primers for the polymerase chain reaction were constructed using an online Primer 3 software. The specificity of the designed primers was checked by Primer-BLAST software.

PCR amplification of the targeted region (from exon 5 to 7) of the PGRN gene was carried out using 2 μL of 50 ng/μL DNA and 0.1 μL each of 20 μM forward (5′-CACCAGCTCCTTGTGTGATG-3′) and reverse (5′-TGGTAGCGTTCTCCTTGGAG-3′) primers. The total volume of each reaction was 20 μL. Amplification was performed using the Molequle-On Thermal Cycler (MOLEQULE-ON, Auckland, New Zealand), in which each reaction was subjected to 94 °C for denaturation and annealing at 61.8 °C, with extension at 72 °C. The obtained products were run on 2% agarose gel alongside a 1 kb marker at 100 V for 40–45 min. The DNA bands were observed on the FastGene® FAS V gel documentation system (Nippon genetics, Germany).

Sequence analysis

The PCR products obtained were purified from the gel via MQ Gel Purification Kit (MOLEQULE-ON, Auckland, New Zealand). The purified products were sequenced via Sanger sequencing technique and were analysed by MEGA X software.

Statistical analysis

The association of SNPs between cases and controls were analysed by Pearson’s Chi-square test. Genotypic and allelic frequencies were determined by direct counting. MedCalc (, an online statistical tool, was employed to calculate the odds ratio (OR) at a 95% confidence interval (CI). The linkage disequilibrium plot and haplotype frequencies were estimated by the SHEsis program ( Genetic models such as dominant, co-dominant, over dominant and recessive models were also tested to determine the genotypic and allelic associations of the identified polymorphisms with susceptibility to psoriasis.


A total of 342 diagnosed psoriasis patients and controls were genotyped in this study. Among the patients, 72% were plaque psoriasis patients, 12% suffered from pustular, 11% from erythrodermic and 5% patients were from nail psoriasis. According to our data, the highest number of psoriasis cases emerged in the age group of 21–30 years. A detailed account of the baseline demographic characteristics of patients and controls is given in Table 1.

Table 1 The baseline characteristics of Psoriasis patients and controls

Although plaque psoriasis was the most prevalent type, some variations were observed in the clinical presentation of the disease among patients. Many patients exhibited large, asymmetrical lesions with thick white plaques, on their knees, elbows and lower backs (Fig. 2a), while some patients demonstrated small, circular lesions with thin silver plaques distributed non-uniformly on their arms and legs (Fig. 2b and c).

Fig. 2
figure 2

Psoriasis vulgaris, commonly termed as plaque-type psoriasis, exists in varying clinical forms. a Chronic plaque psoriasis with thick white plaque on the lower back. b Symmetrical lesions distributed non-uniformly on the fore-arm. c Erythematous and extensively confluent plaques on the leg

PGRN gene polymorphisms

Amplification of the exon 5–7 of the PGRN gene produced a single band on the agarose gel, with a product size of 978 bp, which was purified for sequence analysis. Two PGRN variants, rs25646 and rs850713, were identified in psoriasis patients, as indicated in Fig. 3. In addition, an unknown point mutation, c.805 A/G, located at intron 7 was also identified (Table 2).

Fig. 3
figure 3

Electropherograms indicating change in nucleotide sequence of PGRN gene. a A single blue peak at exon 5 indicates change of nucleotide from T to C (rs25646). b A change of nucleotide from G to A observed in rs850713. c A novel point mutation observed at intron 7 (805 A/G). The double peak observed indicates heterozygosity

Table 2 Summary of variants of PGRN gene in psoriasis patients and controls

Frequency distribution

Genotype distribution of the PGRN polymorphisms between psoriasis patients and controls is presented in Table 3. The homozygous mutant CC genotype of rs25646 was highly prevalent in patients as compared to the controls, and the wildtype T allele was present abundantly in controls while the mutant C allele was abundant in patients.

Table 3 Genotypic frequencies and association analysis of SNPs among psoriasis patients

For rs850713, the homozygous variant AA genotype was higher among patients, while the wildtype GG genotype was observed in a majority of controls. The allelic distribution showed that the mutant A allele had a higher frequency in cases, whereas the G allele was higher in controls. The novel variant, 805A/G existed mostly in heterozygous condition (AG genotype) in 36.8% of cases and 14% of controls.

Association analysis

Pearson’s chi square test revealed that rs25646 and rs850713 were associated with the disease (Table 3). The odds ratio values indicated that rs25646 (p <  0.001, OR = 6.217, 95% CI = 3.34–11.57), rs850713 (p <  0.001, OR = 6.668, 95% CI = 3.512–12.66) and the unreported SNP 805A/G (p = 0.017, OR = 2.875, 95% CI = 1.201–6.883) were significantly associated with the risk of disease.

Genetic model and linkage analysis

Genetic models identify the potential role of genotypes with respect to disease pathogenesis. Genetic modelling was performed for each genotype observed, and OR was calculated to evaluate the impact of each allelic combination on disease onset. The genotype association analysis of rs25646 showed that the CC genotype in dominant, recessive and codominant forms was linked with an increased risk of disease (Table 4). Similarly, the AA genotype of rs850713 was significantly associated with the risk of disease in dominant and codominant conditions. For the novel SNV, the heterozygous AG genotype was associated with an increased risk of psoriasis in codominant and over-dominant conditions.

Table 4 The analysis of inheritance mode for the genotypes of SNPs between psoriasis patients and controls

The multi-SNP association analysis between rs25646, rs850713 and the point mutation is indicated in Table 5. Odds ratio confirm the role of CAA (OR = 8.085, 95% CI = 5.16–12.66) and the CAG (OR = 3.204, 95% CI = 1.97–5.21) haplotypes with the risk of psoriasis progression. While the TGA (OR = 0.19, 95% CI = 0.14–0.26) and the CGA (OR = 0.46, 95% CI = 0.23–0.91) haplotypes showed a protective effect among patients. The linkage disequilibrium plot suggested that the SNPs were in strong LD, and are likely to be inherited together (Fig. 4).

Table 5 Haplotypes of SNPs in patients and controls
Fig. 4
figure 4

Linkage disequilibrium analysis for rs25646, rs850713 and the point mutation 805 A/G


Lesional psoriatic skin displays elevated PGRN levels in the epidermis and the infiltrating inflammatory cells, and overexpression of the protein suppresses the production of inflammatory cytokines, which include IL-1β, IL-6, COX-2 and IFN-γ [13, 23, 30]. Genetic variations in the PGRN gene can potentially dysregulate the anti-inflammatory potential, modify the expression pattern of the protein and may contribute to the initiation of diseases. In the current study, the polymorphisms rs25646 and rs850713 in the PGRN gene were investigated in diagnosed psoriasis patients and controls.

The SNP rs25646 (c.384 T/C), present on exon 5 of PGRN, is a missense mutation where the codon GAT is replaced by GAC. However, no change in the amino acid sequence is observed as both the codons code for aspartic acid (p.D128D). Genotypic analysis revealed that the mutant allele (C) existed frequently in cases (65%) and the wildtype T allele was frequent among controls (76%). However, a study conducted on the AS patients of the Chinese Han population reported contrasting results, where the mutant C allele was abundant in controls (16.7%) as compared to the cases (14.6%), thus suggesting that the SNP had no impact on AS susceptibility [25]. In the current study, the wildtype TT genotype was observed in 63.7% of the controls and 26% of cases, while the mutant CC genotype occurred in 56% of cases and 10.5% of controls. The heterozygous TC genotype was observed to exist more frequently in controls (25.7%) as compared to cases (17.5%) (Table 3). The SNP rs25646 was found to be significantly associated with the risk of disease development and progression. To further investigate the role of each genotype in the pathogenesis of psoriasis, genetic models were applied. It was observed that the dominant, co-dominant and recessive CC genotypes confer a higher risk of psoriasis among cases (Table 4). Whereas the TC genotypes were negatively associated with disease progression. Although no amino acid change was observed as the consequence of the studied SNP rs25646, such variations can disrupt the gene expression and may alter the structure and function of the protein [31], thus leading to disease development.

In this study, rs850713 also showed significant association with the risk of psoriasis onset and progression. This SNP results in the substitution of G to A. As denoted in Table 3, the frequency of the homozygous mutant genotype (AA) and the heterozygous GA genotype was higher in patients, 51.5 and 19%, as compared to the control subjects, 16.9 and 3.5% respectively. Comparable results were obtained in another study involving GD patients [19], where the GA genotype existed in 52% of the cases and 43% controls. The genetic models constructed for rs850713 (Table 4), suggested that GA and AA genotypes significantly contribute to the increased risk of developing psoriasis. These results predicted that the variant allele A is highly pathogenic and may have the potential to alter the splicing region and cause protein degradation, possibly due to misfolding.

Genetic analysis of the novel variant 805A/G revealed that the wildtype AA genotype was higher in frequency in both cases and controls, while the heterozygous AG genotype existed in 36.8% of cases and 14% controls and the homozygous mutant genotype (GG) was observed in 1.75% of patients and 0.6% controls. The distribution of 805A/G genotypes between diagnosed psoriasis patients and controls exhibited a significant association with the risk of disease development and progression in over-dominant and codominant AG genotypic forms. Whereas the GG genotype in recessive (AA + AG vs. GG) and codominant (AA + GG vs. AG) showed a significant negative association with psoriasis (Table 4). Thus, demonstrating that the G allele increases the risk of disease when it occurs in heterozygous form only. Although these variants seem benign, they may be involved in disease pathogenesis by altering the enhancer or silencer regions of the gene, thereby causing exon skipping leading to functional changes [32].

Previous reports highlighting the link between PGRN deficiency and psoriasis severity indicate that serum progranulin levels are negatively correlated with PASI scores [13]. Several studies have shown that serum and plasma PGRN levels are significantly lower in mutation carriers as compared to non-carriers [33]. SNPs can alter the expression of the PGRN gene and have been proposed as risk factors for neurodegenerative diseases such as frontotemporal lobar degeneration (FTLD) [34], Alzheimer’s [35], Gaucher’s [19] as well as tumor progression [24], inflammatory arthritis and psoriasis. However, Hu et al., [25] did not find a significant association between PGRN mutations and ankylosing spondylitis in the Chinese Han population.

Multi-SNP analysis between the three identified variants of PGRN gene exhibited that the CAA and CAG haplotypes were significantly associated with increasing the risk of psoriasis development and progression (Table 5). Linkage disequilibrium plot (Fig. 4) also verified that the detected SNPs, rs25646 and rs850713 were 81% (D′ = 0.81) associated, while the probability of inheriting the novel point mutation 805A/G with rs25646 and rs850713 were 94% (D′ = 0.94) and 79% (D′ = 0.79) respectively. These high associations are due to the presence of the variations on the same chromosome.

In light of the obtained results, the identification of PGRN gene polymorphisms provide a better understanding of the influence of gene variants on psoriasis pathogenesis. As the haplotype analysis demonstrated, the risk haplotypes may be useful in predicting the disease and its associated comorbidities in individuals at risk or have a history of psoriasis in their families. Similar studies exploring other regions of the gene coupled with expression analysis may help predict the role of PGRN as a possible biomarker for psoriasis.


Progranulin plays a critical role as an anti-inflammatory agent by modulating the signalling pathways. The current study demonstrated the possible association of genetic variations (rs25646, rs850713 and the novel variant 805 A/G) in the PGRN gene with psoriasis pathogenesis. The CAA and CAG haplotypes were found to be significantly associated with the development of psoriasis. The identified PGRN gene variations may be involved in downregulation of the protein at serum level, thus interfering with the therapeutic potential of progranulin and increase the risk of developing susceptibility to psoriasis. Furthermore, the study suggests that genetic analysis of the PGRN gene in psoriasis patients may present a potential clinical approach for better screening, intervention and management of the disease.

Availability of data and materials

All data generated or analyzed during this study are included in this published article.


  1. World Health Organization. Global Report on Psoriasis. 2018. Retrieved from:

    Google Scholar 

  2. Grän F, Kerstan A, Serfling E, Goebeler M, Muhammad K. Focus: skin: current developments in the immunology of psoriasis. Yale J Biol Med. 2020;93:97–110 PMID: 32226340.

    PubMed  PubMed Central  Google Scholar 

  3. Griffiths CE, Barker JN. Pathogenesis and clinical features of psoriasis. Lancet. 2007;370:263–71.

    Article  CAS  PubMed  Google Scholar 

  4. Higgins E. Psoriasis. Medicine. 2021;49:361–9.

    Article  Google Scholar 

  5. Woo Y, Cho D, Park H. Molecular mechanisms and management of a cutaneous inflammatory disorder: psoriasis. Int J Mol Sci. 2017;18:2684–710.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Ayala-Fontánez N, Soler DC, McCormick TS. Current knowledge on psoriasis and autoimmune diseases. Psoriasis. 2016;6:7–32.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Kamiya K, Kishimoto M, Sugai J, Komine M, Ohtsuki M. Risk factors for the development of psoriasis. Int J Mol Sci. 2019;20:4347–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Zeng J, Luo S, Huang Y, Lu Q. Critical role of environmental factors in the pathogenesis of psoriasis. J Dermatol. 2017;44:863–72.

    Article  PubMed  Google Scholar 

  9. Merve HM, Sevilay K, Sibel O, Başak B, Ceren CG, Demirci T, Cüneyt A. Psoriasis and genetics. Interdiscip Approach Psoriasis. 2017;1:1–12.

    Article  CAS  Google Scholar 

  10. Chiricozzi A, Romanelli P, Volpe E, Borsellino G, Romanelli M. Scanning the immunopathogenesis of psoriasis. Int J Mol Sci. 2018;19:179–210.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Di Meglio P, Nestle FO. Immunopathogenesis of psoriasis. Clin Basic Immunodermatol. 2017;21:373–95.

    Article  Google Scholar 

  12. Rioux G, Ridha Z, Simard M, Turgeon F, Guérin FL, Pouliot R. Transcriptome profiling analyses in psoriasis: a dynamic contribution of keratinocytes to the pathogenesis. Genes. 2020;11:1155–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Huang K, Chen A, Zhang X, Song Z, Xu H, Cao J, Yin Y. Progranulin is preferentially expressed in patients with psoriasis vulgaris and protects mice from psoriasis-like skin inflammation. Immunology. 2015;145:279–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Goldminz AM, Au SC, Kim N, Gottlieb AB, Lizzul PF. NF-κB: an essential transcription factor in psoriasis. J Dermatol Sci. 2013;69:89–94.

    Article  CAS  PubMed  Google Scholar 

  15. Ogawa E, Sato Y, Minagawa A, Okuyama R. Pathogenesis of psoriasis and development of treatment. J Dermatol. 2018;45:264–72.

    Article  CAS  PubMed  Google Scholar 

  16. Sellati TJ, Sahay B. Cells of innate immunity: mechanisms of activation. In: McManus LM, Mitchell RN, editors. Reference module in biomedical sciences: pathobiology of human disease. Academic Press; 2014. p. 258–74.

    Chapter  Google Scholar 

  17. Abella V, Pino J, Scotece M, Conde J, Lago F, Gonzalez-Gay MA, Mera A, Gómez R, Mobasheri A, Gualillo O. Progranulin as a biomarker and potential therapeutic agent. Drug Discov Today. 2017;22:1557–64.

    Article  CAS  PubMed  Google Scholar 

  18. Egashira Y, Suzuki Y, Azuma Y, Takagi T, Mishiro K, Sugitani S, Hara H. The growth factor progranulin attenuates neuronal injury induced by cerebral ischemia-reperfusion through the suppression of neutrophil recruitment. J Neuroinflammation. 2013;10:1–13.

    Article  CAS  Google Scholar 

  19. Jian J, Zhao S, Tian QY, Liu H, Zhao Y, Chen WC, Grunig G, Torres PA, Wang BC, Zeng B, Pastores G, Liu CJ. Association between progranulin and Gaucher disease. EBioMedicine. 2016;11:127–37.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Lan YJ, Sam NB, Cheng MN, Pan HF, Gao J. Progranulin as a potential therapeutic target in immune-mediated diseases. J Inflamm Res. 2021;14:6543–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Liu C, Li J, Shi W, Zhang L, Liu S, Lian Y, Liang S, Wang H. Progranulin regulates inflammation and tumor. Anti-Inflamm Anti-Allergy Agents Med Chem. 2020;19:88–102.

    Article  CAS  Google Scholar 

  22. Tang W, Lu Y, Tian QY, Zhang Y, Guo FJ, Liu GY, Liu CJ. The growth factor progranulin binds to TNF receptors and is therapeutic against inflammatory arthritis in mice. Science. 2011;332:478–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Farag AGA, Shoaib MA, Samaka RM, Abdou AG, Mandour MM, Ibrahim RAL. Progranulin and beta-catenin in psoriasis: an immunohistochemical study. J Cosmet Dermatol. 2019;18:2019–26.

    Article  PubMed  Google Scholar 

  24. Bateman A, Cheung ST, Bennett HP. A brief overview of progranulin in health and disease. Progranulin. 2018;3-15

  25. Hu N, Cui Y, Yang Q, Wang L, Yang X, Xu H. Association of polymorphisms in TNF and GRN genes with ankylosing spondylitis in a Chinese Han population. Rheumatol Int. 2018;38:481–7.

    Article  CAS  PubMed  Google Scholar 

  26. Hawkes JE, Chan TC, Krueger JG. Psoriasis pathogenesis and the development of novel targeted immune therapies. J Allergy Clin Immunol. 2017;140:645–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Rendon A, Schäkel K. Psoriasis pathogenesis and treatment. Int J Mol Sci. 2019;20:1475.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Sfikakis PP, Tsokos GC. Towards the next generation of anti-TNF drugs. Clin Immunol. 2011;141:231–5.

    Article  CAS  PubMed  Google Scholar 

  29. MWer S, Dykes D, Polesky H. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988;16:1215.

    Article  Google Scholar 

  30. Tian R, Li Y, Yao X. PGRN suppresses inflammation and promotes autophagy in keratinocytes through the Wnt/β-catenin signaling pathway. Inflammation. 2016;39:1387–94.

    Article  CAS  PubMed  Google Scholar 

  31. Zeng Z, Bromberg Y. Predicting functional effects of synonymous variants: a systematic review and perspectives. Front Genet. 2019;10:1–15.

    Article  CAS  Google Scholar 

  32. Cooper DN. Functional intronic polymorphisms: buried treasure awaiting discovery within our genes. Hum Genomics. 2010;4:1–5.

    Article  CAS  Google Scholar 

  33. Thurner L, Zaks M, Preuss KD, Fadle N, Regitz E, Ong MF, Pfreundschuh M, Assmann G. Progranulin antibodies entertain a proinflammatory environment in a subgroup of patients with psoriatic arthritis. Arthritis Res Ther. 2013;15:1–9.

    Article  CAS  Google Scholar 

  34. Karch CM, Ezerskiy L, Redaelli V, Giovagnoli AR, Tiraboschi P, Pelliccioni G, Pelliccioni P, Kapetis D, D’Amato I, Piccoli E, Ferretti MG, Rossi G. Missense mutations in progranulin gene associated with frontotemporal lobar degeneration: study of pathogenetic features. Neurobiol Aging. 2016;38:215e1-21e12.

    Article  CAS  Google Scholar 

  35. Fenoglio C, Galimberti D, Cortini F, Kauwe JS, Cruchaga C, Venturelli E, Scarpini E. rs5848 variant influences GRN mRNA levels in brain and peripheral mononuclear cells in patients with Alzheimer’s disease. J Alzheimers Dis. 2009;18:603–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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We would like to express our deep gratitude to the hospital staff at Jinnah Post Graduate Medical Centre (JPMC) Karachi, for their help in sample collection. We also appreciate the efforts of Ms. Oniba Khalid and Ms. Sidra Kawal for data analysis and manuscript editing.


The authors declare no specific funding for this work.

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SS conceptualized and designed the methodology of the study. ZI performed investigation, formal analysis, and prepared the manuscript. AS and BK provided samples. SZ provided resources and reviewed the manuscript. AA provided supervision. All authors have read and approved the final manuscript.

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Correspondence to Saima Saleem.

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Informed written consent to participate was taken from all participants to participate in the study. The study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki and all procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional review board of The Karachi Institute of Biotechnology and Genetic Engineering (KIBGE) and Jinnah Post Graduate Medical Centre (JPMC) (Ref No.F.2–81/2021-GENL/58186/JPMC).

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Saleem, S., Imran, Z., Samdani, A. et al. Mutations in PGRN gene associated with the risk of psoriasis in Pakistan: a case control study. BMC Med Genomics 16, 335 (2023).

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