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 Table of Contents  
ORIGINAL ARTICLE
Year : 2018  |  Volume : 38  |  Issue : 1  |  Page : 12-17

Association of proinflammatory cytokine tumor necrosis factor-α gene promoter -308 and -238 polymorphism with psoriasis in North Indian population


1 Department of Human Genetics, Punjabi University, Patiala, Punjab; Department of Biochemistry, University of Kashmir, Srinagar, Jammu and Kashmir, India
2 Center of Research for Development (CORD), University of Kashmir, Srinagar, Jammu and Kashmir, India
3 Department of Human Genetics, Punjabi University, Patiala, Punjab, India
4 Department of Dermatology, Venereology and Leprology, Post Graduate Institute of Medical Education and Research, Chandigarh, India

Date of Submission10-May-2017
Date of Acceptance11-Oct-2017
Date of Web Publication12-Mar-2018

Correspondence Address:
Rajinder Kaur
Department of Human Genetics, Punjabi University, Patiala, Punjab
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ejdv.ejdv_23_17

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  Abstract 


Background/objective Tumor necrosis factor (TNF) is an important proinflammatory cytokine that plays a role in the pathogenesis of psoriasis. The aim of the present study was to investigate the role of TNF-α −308G/A and TNF-α −238G/A polymorphism, haplotype, and serum level in the pathogenesis of psoriasis.
Materials and methods A total of 200 psoriatic patients and 200 controls were genotyped for TNF-α −308G/A and TNF–α −238G/A polymorphism by using polymerase chain reaction. In addition, serum levels of TNF-α were measured by enzyme-linked immunosorbent assay.
Results Polymorphism of TNF–α −308 was found to be associated with a decreased risk for psoriasis odds ratio=0.29; (95% confidence interval=0.14–0.62), and polymorphism of TNF–α −238 was associated with an increased risk for psoriasis odds ratio=37.81; (95% confidence interval=12.77–112.01). HT2 GA haplotype was found to be associated with an increased risk for psoriasis. Moreover, the serum TNF-α level increased in patients compared with controls, with a significant correlation between serum TNF-α and psoriasis severity.
Conclusion Our findings suggested that TNF-α polymorphisms imparted significant risk toward the development of psoriasis in north Indian population.

Keywords: cytokine, polymorphism, psoriasis, tumor necrosis factor


How to cite this article:
Aadil W, Ganai BA, Akhtar T, Narang T, Kaur R. Association of proinflammatory cytokine tumor necrosis factor-α gene promoter -308 and -238 polymorphism with psoriasis in North Indian population. Egypt J Dermatol Venerol 2018;38:12-7

How to cite this URL:
Aadil W, Ganai BA, Akhtar T, Narang T, Kaur R. Association of proinflammatory cytokine tumor necrosis factor-α gene promoter -308 and -238 polymorphism with psoriasis in North Indian population. Egypt J Dermatol Venerol [serial online] 2018 [cited 2018 Aug 19];38:12-7. Available from: http://www.ejdv.eg.net/text.asp?2018/38/1/12/227093




  Introduction Top


Psoriasis is known as chronic immune-mediated inflammatory skin disease affecting about 3% of the world’s population [1],[2]. Previous studies suggest that psoriatic skin is recognized by clinical presentation of red, scaly plaques containing numerous and dense infiltrates of immune cells that can produce many cytokines and inflammatory molecules [1],[3],[4]. Increasing knowledge about disease-specific immunologic abnormalities and the genetic control of immunoregulatory mechanisms such as the production of protective or harmful cytokines has been of great advantage in studying genetic factors associated with diseases like allergic asthma, rheumatoid arthritis, and lupus erythematosus [5],[6]. Such an approach may also be considered when investigating the genetics of psoriasis, the psoriatic inflammatory process being characterized by a disturbance of the local cytokine network with overexpression of proinflammatory mediators, such as tumor necrosis factor-α (TNF-α) [7],[8]. The genetic landscape of psoriasis is dominated by major histocompatibility complex HLA-Cw*0602 [9],[10] and the genes encoding TNF-α [11],[12]. The TNF-α gene is located on the major histocompatibility complex region, which is only 250 kb centromeric from the human leukocyte antigen-B, showing its presence on the short arm of chromosome 6 (6p21.3). This region is polymorphic, with up to 44 polymorphisms reported [12]. Two single-nucleotide polymorphisms involving GA transitions in the promoter region at the −238 and −308 sites have been shown to influence TNF-α expression and have been found associated with the development of psoriasis [11],[13],[14],[15]. On the basis of the above studies, we designed this study to investigate whether the polymorphisms of TNF-α −308G/A and TNF-α −238G/A and serum levels may be risk factors for the development of psoriasis in north Indian psoriatic patients and to establish possible allelic and genetic differences between them and healthy controls and its relation to TNF-α serum levels with the severity of psoriasis.


  Materials and methods Top


Participants recruitment

This hospital based case–control study was conducted after approval by the institutional ethical committee and the participants were included only after they willingly decided to become part of the study. An informed consent form was filled and signed by all the participants. The study was conducted over the period of 15 months starting from July 2014 to October 2015 and included 200 clinically diagnosed (by dermatologist) psoriatic patients. Age (±7 years) and sex matched healthy participants from the same geographical region were included as controls.

Psoriasis Area and Severity Index calculation

Psoriasis Area and Severity Index (PASI) is a widely used tool for the measurement of severity of psoriasis. PASI score was calculated as described in the study by Langley and Ellis [16]. A higher PASI score represents a greater degree of psoriatic severity [17].

Blood sampling

A volume of 5 ml of venous blood were taken by trained laboratory technician, out of which 2 ml were taken in a sterile EDTA coated vials for genomic DNA extraction and the remaining 3 ml was centrifuged at 4000 rpm for 5 min. The serum was taken out and stored at −80°C till analysis.

Genomic DNA extraction

Genomic DNA was isolated from the blood samples by using the phenol–chloroform method [18] and the isolated DNA was stored at −20°C for future use.

Genotyping of tumor necrosis factor-α 308

For the detection of SNPs in TNF the amplification refractory mutation system-PCR method was applied, as described by Karma et al. [19]. The primers forward: 5′-CTGCATCCCCGTCTTTCTCC-3′, reverse 1: 5′-ATAGGTTTTGAGGGGCATCG-3′, and reverse 2: 5′-ATAGGTTTTGAGGGGCATCA-3′ were used. PCR was performed at at 96°C for 3 min (initial denaturation) followed by 30 cycles at 96°C for 45 s (denaturation), 55°C for 80 s (annealing), and 72°C for 2 min (extension). A final extension step was carried out at 72°C for 3 min. PCR products (836 bp) were separated on 2% agarose stained with ethidium bromide and analyzed by using ultraviolet transilluminator. Positive amplification of one allele indicates homozygosity for that allele, whereas positive amplification of both alleles indicates heterozygosity of both alleles. To assess the success of PCR amplification in both reactions, an internal control was amplified using a pair of primers − forward primer: 5′-CCTTCCAACCATTCCCTTA-3′ and reverse primer: 5′-TCACGGATTTCTGTTGTGTTTC-3′ − from the nucleotide sequence of the human growth hormone.

Genotyping of tumor necrosis factor-α 238

The primer pair used for the amplification of TNF-α 238 was 5′-AAACAGACCACAGACCTGGTC-3′ (forward primer) and 5′-AGGATACCCACACTCCCCATCCTCCCGGATC-3′ (reverse primer) to assess polymorphism. The conditions for the TNF-α −238 polymorphism were as follows: denaturing step at 95°C for 5 min followed by 35 cycles at 95°C for 40 s, 61°C for 1 min, 72°C for 40 s, and finally 72°C for 10 min. The final PCR product of 165 bp was obtained and was digested by a restriction enzyme (BamHI at 37°C for 3 h; fermntas). Digested products were separated on 3% agarose gel. The digestion of the fragments (165 bp) revealed products of 123 bp and 42 bp (allele G) and 165 bp (allele A).

Measurement of serum tumor necrosis factor concentration

TNF concentration in the serum was determined by using a double antibody sandwich ELISA kit provided by Krishgen Biosystem (Whittier, California, USA), followed the manufacturer’s instructions by using standard curve.

Statistical analysis

Odds ratio (OR) with 95% confidence limits, calculated by using logistic regression, was used to assess the relationship between TNF-α genotypes and risk for psoriasis. A P value of less than 0.005 was taken as statistically significant. All the statistical calculations were done using SNPstat (China) software and VassarStats (USA).


  Results Top


Out of 200 cases recruited in the present study, 130 (65%) were male patients and 70 (35%) were female patients. Their ages ranged from 18 to 70 years with a mean age of 38.61±13.713 years among the psoriatic patients, whereas among controls, the age ranged from 19 to 65 years with a mean age of 36.695±11.4765 years. Thirty-five (16%) psoriatic patients showed a positive family history of psoriasis. The majority of the cases, 57.5%, were from rural areas whereas 42.5% were from urban areas. The mean disease duration was 9.88±8.19 years. The mean BMI of psoriatic patients and controls was 26.94±4.17 and 24.80±4.28 kg/m2, respectively. The mean PASI score for clinical assessment in psoriatic patients was 10.654±9.09 ([Table 1]).
Table 1 Characteristics of the study group

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The allele and genotype frequencies of TNF-α −308 gene in patients and controls are summarized in [Table 2]. The allele A frequency was found to be higher in controls [25.75% (103/400)] as compared with cases [14% (56/400)] OR=0.469; [95% confidence interval (CI)=0.3273–0.6732]. It was observed that AA genotype was higher in controls [15.5% (31/200)] than in cases [7% (14/200)] OR=0.29; (95% CI=0.14–0.62). The polymorphism of TNF-α −308 was found to be associated with a decreased risk for psoriasis (P=0.0012). However, cases had a higher number of G allele, as well genotype GG, which indicates that carriers of this GG genotype are more likely to develop psoriasis. The dominant 0.40 (95% CI=0.23–0.68) and recessive 0.24 (95% CI=0.16–0.72) models show significant association of mutant allele A with a decreased risk for psoriasis. However, over dominant model does not show any association with the risk for psoriasis ([Table 2]).
Table 2 Genotype and allele distribution of tumor necrosis factor-α −308 allele in psoriasis cases and controls

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The allele and genotype frequencies of TNF-α −238 gene in patients and controls are summarized in [Table 3]. The allele A frequency was found to be higher among patients [51.50% (208/400)] as compared with controls [26.25% (105/200)] OR=3.043; (95% CI=2.162–4.049) P=0.001. It was observed that AA genotype was higher among patients [38.5% (77/200)] than among controls [2.5% (5/200)] OR=37.81; (95% CI=12.77–112.01) P=0.001, confirming that TNF-α −238 G/A is associated with an increased risk for psoriasis. The dominant OR=2.34 (95% CI=1.44–3.79) and recessive OR=39.63 (95% CI=13.83–113.54) models also showed significant association of mutant allele A with an increased risk for psoriasis ([Table 3]). SNP–SNP interaction did not show any modulating effect as the test of interaction was statistically nonsignificant (P=0.74) ([Table 4]). The haplotype frequencies of psoriasis patients and controls are summarized in [Table 5]. The pair-wise LD matrix demonstrated that the nearly complete LD (D>0<1) (D, between 0.20 and 0.45) existed between the polymorphism of position −308 and 238 within the TNF-α gene. The presence of four haplotypes with a frequency of more than or equal to 1 was estimated. The haplotypes accounted for 90% of all haplotypes in the pooled samples. Psoriasis patients had a significantly increased frequency of HT2 GA haplotype (P=0.001) OR=2.52 (95% CI=0.28–0.79), which confirms that HT2 GA haplotype is associated with an increased risk for psoriasis, and haplotype HT3 AG OR 0.47 (95% CI: 1.30–3.70; P=0.0045) shows a decreased risk for psoriasis among patients hailing from North India.
Table 3 Genotype and allele distribution of tumor necrosis factor-α −238 allele in psoriasis cases and controls

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Table 4 SNP–SNP interaction between tumor necrosis factor-α 308 and tumor necrosis factor-α 238 polymorphism of tumor necrosis factor-α gene

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Table 5 Possible haplotype frequencies of tumor necrosis factor–α gene in cases and controls

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TNF-α serum level in psoriasis patients were significantly elevated (225±22.82 pg/ml) as compared with controls (69.80±10.02 pg/ml). Statistically significant differences were observed after data analysis (P=0.02). In addition, we observed a significant correlation between the TNF-α serum level and disease severity PASI score (P=0.03) ([Table 6]).
Table 6 Correlation between serum levels of psoriasis patients and control and its relation with Psoriasis Area and Severity Index

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  Discussion Top


Psoriasis is an inflammatory dermatosis that is multifactorial and has a strong polygenic genetic basis [10],[20]. TNF gene has been recognized as candidate gene in immune-mediated disorders including psoriasis [21],[22]. In the present study we determined the association of TNF-α −308 and TNF-α −238 cytokine polymorphisms and their serum levels with the severity of psoriasis in the North Indian population. Transition of single nucleotide from guanine (G) to adenine (A) at position −308 is the most common in general populations. This change has impact on the expression of TNF-α gene in which there is about six-fold increased transcriptional activity and higher levels of TNF-α [23]. Therefore, the genetic polymorphisms in TNF-α gene can have some effects on the hosts’ susceptibility to psoriasis by the changed TNF-α expression. As regards TNF-α −308, our results demonstrated increase in the G allele and GG genotype in psoriasis patients compared with the control group. On the other hand, the increased frequency of A allele and AA genotype in the control group compared with the psoriasis patients’ group confirmed that this mutant genotype plays a protective role in psoriasis. In agreement with our results, some earlier studies have found a higher frequency of TNF-α −308 GG in moderate to severe psoriasis patients [24] or a higher frequency of the TNF-α −308G allele in patients with early-onset psoriasis [25],[26]. However, other investigators reported no difference in the distribution of TNF-α alleles or genotypes between patients and controls [25],[27],[28]. Our results substantiate early findings in which it has been reported that TNF-α −308 G/A polymorphism is associated with a decreased risk for psoriasis in both Caucasian and Asian populations [21],[29]. We observed that the mutant allele TNF-α −238A occurred more frequently in patients with psoriasis compared with controls, which confirms that TNF-α −238 G/A polymorphism is associated with an increased risk for psoriasis in north Indian population. In their study, Rahman et al. [30] revealed that TNF-α −238G/A polymorphism as a risk factor for psoriasis in Egyptian population. A meta-analysis by Zhuang et al. [21] suggested that TNF-α −238G/A is associated with a risk for psoriasis in different populations. In contrast to our results, some previous studies concluded that the −238GG genotype is more frequent among individuals with more severe forms of psoriasis [14]. Some studies have observed these differences only in patients with early-onset psoriasis [26] or only in male patients [31]. Our study also revealed elevated serum level of TNF-α in psoriasis patients when compared with the control group. Our findings are in agreement with many previously conducted studies [19],[32],[33]. Jacob et al. [34] found no differences in TNF-α levels between patients and controls. The difference in severity level (PASI) was found to be significantly correlated with serum TNF-α level (P=0.03), proving the role of these cytokines as main parameters for disease severity. The study by Takahashi et al. [35] revealed that serum level of TNF-α was markedly elevated in psoriatic patients as compared with healthy controls; elevated levels were also correlated with PASI. Interestingly, the HT2 GA haplotype of TNF gene was associated with an increased risk for psoriasis, which substantiates early finding by Weissensteiner et al. [36]. In summary, TNF-α 308 G/A polymorphism plays a protective role in psoriasis and TNF-α 238 G/A polymorphism is associated with an increased risk for psoriasis; furthermore, the serum level was significantly increased in psoriasis patients compared with controls, with a correlation between serum levels and disease severity. Highlighting the role of cytokines in the pathogenesis of psoriasis is important for the development of a database, maintenance, and resolution of lesions. Therefore, anti-TNF therapy may be helpful in controlling the pathogenesis of psoriasis. However, because of a small sample size (a limitation of the study) we recommend future studies with a larger size to ascertain our findings.

Acknowledgements

The authors thank the Indian Council of Medical Research, New Delhi, India for providing financial support in the form of major research (No. 61/13/2011-BMS), sanctioned to Dr Rajinder Kaur, Department of Human Genetics, Punjabi University, Patiala, Punjab.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Nestle FO, Di Meglio P, Qin J-Z., Nickoloff BJ. Skin immune sentinels in health and disease. Nat Rev Immunol 2009; 9:679–691.  Back to cited text no. 1
    
2.
Menter A, Griffiths CE. Current and future management of psoriasis. Lancet 2007; 370:272–284.  Back to cited text no. 2
    
3.
Nickoloff BJ, Nestle FO. Recent insights into the immunopathogenesis of psoriasis provide new therapeutic opportunities. J Clin Invest 2004; 113:1664–1675.  Back to cited text no. 3
    
4.
Griffiths CE, Barker JN. Pathogenesis and clinical features of psoriasis. Lancet 2007; 370:263–271.  Back to cited text no. 4
    
5.
Eskdale J, Gallagher G, Verweij CL, Keijsers V, Westendorp RG, Huizinga TW. Interleukin 10 secretion in relation to human IL-10 locus haplotypes. Proc Natl Acad Sci 1998; 95:9465–9470.  Back to cited text no. 5
    
6.
Mok CC, Lanchbury JS, Wai Chan D, Lau CS. Interleukin‐10 promoter polymorphisms in Southern Chinese patients with systemic lupus erythematosus. Arthritis Rheum 1998; 41:1090–1095.  Back to cited text no. 6
    
7.
Uyemura K, Yamamura M, Fivenson DF, Modlin RL, Nickoloff BJ. The cytokine network in lesional and lesion-free psoriatic skin is characterized by a T-helper type 1 cell-mediated response. J Invest Dermatol 1993; 101:701–705.  Back to cited text no. 7
    
8.
Schlaak JF, Buslau M, Jochum W, Hermann E, Girndt M, Gallati H et al. T cells involved in psoriasis vulgaris belong to the Th1 subset. J Invest Dermatol 1994; 102:145–149.  Back to cited text no. 8
    
9.
Valdimarsson H. The genetic basis of psoriasis. Clin Dermatol 2007; 25:563–567.  Back to cited text no. 9
    
10.
Greb JE, Goldminz AM, Elder JT, Lebwohl MG, Gladman DD, Wu JJ et al. Psoriasis. Nat Rev Dis Primers 2016; 2: 16082.  Back to cited text no. 10
    
11.
Baran W, Szepietowski J, Mazur G, Baran E. A-308 promoter polymorphism of tumor necrosis factor alpha gene does not associate with the susceptibility to psoriasis vulgaris. No difference either between psoriasis type I and type II patients. Acta Dermatovenerol Alp Pannonica Adriat 2006; 15:113–118.  Back to cited text no. 11
    
12.
Llanos C, Soto L, Sabugo F, Bastías M, Salazar L, Aguillón J et al. The influence of-238 and-308 TNF alpha polymorphisms on the pathogenesis and response to treatment in rheumatoid arthritis. Rev Med Chil 2005; 133:1089–1095.  Back to cited text no. 12
    
13.
Hashigucci K, Niizeki H, Naruse T, Ota M, Inamoto N, Nishikawa T et al. A clinical feature associated with polymorphisms of the TNF region in Japanese patients with palmoplantar pustulosis. Hum Immunol 2003; 64:530–537.  Back to cited text no. 13
    
14.
Mössner R, Kingo K, Kleensang A, Krüger U, König IR, Silm H et al. Association of TNF-238 and-308 promoter polymorphisms with psoriasis vulgaris and psoriatic arthritis but not with pustulosis palmoplantaris. J Invest Dermatol 2005; 124:282.  Back to cited text no. 14
    
15.
Schmeling H, Wagner U, Peterson A, Horneff G. Tumor necrosis factor alpha promoter polymorphisms in patients with juvenile idiopathic arthritis. Clin Exp Rheumatol 2006; 24:103.  Back to cited text no. 15
    
16.
Langley RG, Ellis CN. Evaluating psoriasis with psoriasis area and severity index, psoriasis global assessment, and lattice system physician’s global assessment. J Am Acad Dermatol 2004; 51:563–569.  Back to cited text no. 16
    
17.
Kingo K, Koks S, Silm H, Vasar E. IL-10 promoter polymorphisms influence disease severity and course in psoriasis. Genes Immun 2003; 4:455–457.  Back to cited text no. 17
    
18.
Sambrook J, Russell DW. Purification of nucleic acids by extraction with phenol: chloroform. CSH Protoc 2006; 1:pii.  Back to cited text no. 18
    
19.
Karam RA, Zidan HE, Khater MH. Polymorphisms in the TNF-α and IL-10 gene promoters and risk of psoriasis and correlation with disease severity. Cytokine 2014; 66:101–105.  Back to cited text no. 19
    
20.
Piruzian E, Ishkin A, Nikol’skaya T, Abdeev R, Bruskin S. A comparative analysis of the molecular genetic processes in the pathogenesis of psoriasis and Crohn’s disease. Mol Biol 2009; 43:159–165.  Back to cited text no. 20
    
21.
Zhuang L, Ma W, Cai D, Zhong H, Sun Q. Associations between tumor necrosis factor-α polymorphisms and risk of psoriasis: a meta-analysis. PLoS One 2013; 8:e68827.  Back to cited text no. 21
    
22.
El-Tahan RR, Ghoneim AM, El-Mashad N. TNF-α gene polymorphisms and expression. Springerplus 2016; 5:1508.  Back to cited text no. 22
    
23.
Chandran V, Raychaudhuri SP. Geoepidemiology and environmental factors of psoriasis and psoriatic arthritis. J Autoimmun 2010; 34:J314–J321.  Back to cited text no. 23
    
24.
Settin A, Hassan H, El-Baz R, Hassan T. Association of cytokine gene polymorphisms with psoriasis in cases from the nile delta of egypt. Indian J Dermatol 2011; 56:272.  Back to cited text no. 24
[PUBMED]  [Full text]  
25.
Craven N, Jackson C, Kirby B, Perrey C, Pravica V, Hutchinson I et al. Cytokine gene polymorphisms in psoriasis. Br J Dermatol 2001; 144:849–853.  Back to cited text no. 25
    
26.
Reich K, Zipprich S, Fuchs T, Neumann C, Westphal G, Schulz T et al. Combined analysis of polymorphisms of the tumor necrosis factor-α and interleukin-10 promoter regions and polymorphic xenobiotic metabolizing enzymes in psoriasis. J Invest Dermatol 1999; 113:214–220.  Back to cited text no. 26
    
27.
Wongpiyabovorn J, Hirankarn N, Ruchusatsawat K, Yooyongsatit S, Asawanonda P, Poovorawan Y. Association of the interleukin‐10 distal promoter (‐2763A/C) polymorphism with late‐onset psoriasis. Clin Exp Dermatol 2008; 33:186–189.  Back to cited text no. 27
    
28.
Gallo E, Cabaleiro T, Román M, Abad-Santos F, Daudén E. Study of genetic polymorphisms in the tumor necrosis factor α promoter region in Spanish patients with psoriasis. Actas Dermosifiliogr 2012; 103:301–307.  Back to cited text no. 28
    
29.
Li C, Wang G, Gao Y, Liu L, Gao T. TNF-α gene promoter-238G> A and-308G> A polymorphisms alter risk of psoriasis vulgaris: a meta-analysis. J Invest Dermatol 2007; 127:1886–1892.  Back to cited text no. 29
    
30.
Rahman P, Siannis F, Butt C, Farewell V, Peddle L, Pellett F et al. TNFα polymorphisms and risk of psoriatic arthritis. Ann Rheum Dis 2006; 65:919–923.  Back to cited text no. 30
    
31.
Reich K, Hüffmeier U, König IR, Lascorz J, Lohmann J, Wendler J et al. TNF polymorphisms in psoriasis: Association of psoriatic arthritis with the promoter polymorphism TNF* 857 independent of the PSORS1 risk allele. Arthritis Rheum 2007; 56:2056–2064.  Back to cited text no. 31
    
32.
Abanmi A, Al Harthi F, Al Agla R, Ahmad Khan H, Tariq M. Serum levels of proinflammatory cytokines in psoriasis patients from Saudi Arabia. Int J Dermatol 2005; 44:82–83.  Back to cited text no. 32
    
33.
Verghese B, Bhatnagar S, Tanwar R, Bhattacharjee J. Serum cytokine profile in psoriasis-a case-control study in a tertiary care hospital from Northern India. Indian J Clin Biochem 2011; 26:373–377.  Back to cited text no. 33
    
34.
Jacob SE, Nassiri M, Kerdel FA, Vincek V. Simultaneous measurement of multiple Th1 and Th2 serum cytokines in psoriasis and correlation with disease severity. Mediators Inflamm 2003; 12:309–313.  Back to cited text no. 34
    
35.
Takahashi H, Tsuji H, Hashimoto Y, IshidaYamamoto A, Iizuka H. Serum cytokines and growth factor levels in Japanese patients with psoriasis. Clin Exp Dermatol 2010; 35:645–649.  Back to cited text no. 35
    
36.
Weissensteiner T, Lanchbury JS. TNFB polymorphisms characterize three lineages of TNF region microsatellite haplotypes. Immunogenetics 1997; 47:6–16.  Back to cited text no. 36
    



 
 
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