Misbahul Arfin

HLA-DRB1 association in Saudi rheumatoid arthritis patients

Association between HLA-DRB1 alleles and rheumatoid arthritis (RA) has been known for more than three decades. However, the strength of these links varies between ethnic groups. This study examines the frequency of HLA-DRB1 alleles amongst Saudi RA patients. The DRB1 region of major histocompatibility complex was screened by polymerase chain reaction/sequence specific primers (PCR/SSP) in a total of 140 subjects including 70 RA patients and 70 matched healthy controls. HLA-DRB1 *04 was found to be the most frequent allele associated with RA followed by DRB1 *08 and DRB1 *10. On the other hand, the frequency of DRB1*06 was found to be decreased in RA patients as compared to controls. Molecular sub typing of the most prevalent allele DRB1 *04 revealed a statistically significant association between RA and DRB1 *0405. We conclude that an improved understanding about the influence of HLA on RA might help in predicting the susceptibility or protection against disease.

TNF-α and TNF-β Gene Polymorphism in Saudi Rheumatoid Arthritis Patients

Background Tumor necrosis factor (TNF)-α and -β are cytokines with a wide range of inflammatory, apoptotic and immunomodulatory activities. TNF-α promoter –308 G < A polymorphism has been reported to be associated with rheumatoid arthritis (RA) with inconsistent results. Objective The aim of this study is to elucidate a possible association of TNF-α (G–308A) and TNF-β (A+252G) polymorphisms with the susceptibility of RA in Saudi patients. Patients and Methods This case control study consisted of 232 Saudi subjects including 106 RA patients and 126 matched controls. Genomic DNA was extracted using QIAampR DNA mini kit (Qiagen CA, USA). TNF-α and TNF-β genes were amplified using Arms primers. Results The frequencies of TNF-α (–308) allele G and genotype GG were significantly higher in RA patients as compared to controls while allele A and genotype AA were predominant in control group. On the other hand the frequency of TNF-β (+252) GG and AA genotypes were significantly higher in RA patients as compared to controls while GA genotype was predominant in controls. It was inferred that genotype GG positive individuals at position –308 of TNF-α were susceptible to RA while genotype AA might has a protective effect on RA susceptibility in Saudis. Whereas GG and AA genotype of TNF-β at +252 position might exert additive susceptibility to RA and GA might be refractory. However, there was no significant association between duration of morning stiffness, RF positivity and number of joints involved and distribution of alleles/genotypes of TNF-α (–308) or TNF-β (+252) polymorphism. It may be concluded that the TNF-α (–308) and TNF-β (+252) polymorphisms might influence the susceptibility to RA in Saudi population. These results might have prognostic value for future clinical observations.

Association of Interleukin-10 Gene Promoter Polymorphisms in Saudi Patients with Vitiligo

The promoter region of human Interleukin −10 gene is highly polymorphic and has been associated with numerous autoimmune diseases. Recent studies have linked vitiligo with defective autoimmune system. This study is aimed to explore a possible association between IL-10 gene polymorphism and vitiligo in Saudi population. This case control study consisted of 184 Saudi subjects including 83 vitiligo patients (40 males, 43 females mean age 27.85 ± 12.43 years) and 101 matched controls. Genomic DNA was extracted from the blood samples of healthy controls and Vitiligo patients visiting out patient clinic of Department of Dermatology, Riyadh Armed Forces Hospital, using QIA ampR DNA mini kit (Qiagen CA, USA). Interleukin-10 gene was amplified by polymerase chain reaction (PCR) using Arms primers to detect any polymorphism involved at positions −592, −819 and −1082. The frequencies of GG genotype at −1082, and CC genotype at positions −592 and 819 were significantly higher in vitiligo patients compared to healthy subjects suggesting that GG and CC genotypes might be susceptible to vitiligo in Saudis. On the other hand genotypes −1082 GA, −819 CT, and −592 CA of IL-10 were more prevalent in healthy controls suggesting protective effects of GA, CT and CA genotypes against vitiligo. This study indicates that the IL-10 gene may play a significant role in the etiology of vitiligo among Saudis.

TNF-α, TNF-β and IL-10 gene polymorphism and association with oral lichen planus risk in Saudi patients

Objectives Oral lichen planus (OLP) is a chronic inflammatory oral mucosal disease. Cytokines play an important role in the pathogenesis and disease progression of OLP. Various reports have implicated cytokine gene polymorphisms in susceptibility to develop some immune mediated conditions including OLP. The purpose of this study was to investigate the association of tumor necrosis factor (TNF)-α, TNF-β and interleukin (IL)-10 gene polymorphisms with the OLP risk. Material and Methods Forty two unrelated patients with OLP and 211 healthy volunteers were genotyped for TNF-α (-308 G/A), TNF-β (+252A/G), IL-10 (-1082G/A), IL-10 (-819C/T), and IL-10 (-592C/A) polymorphisms. Results The frequencies of allele A and genotype GA of TNF-α (-308G/A) were significantly higher while allele G and GG genotypes were lower in OLP patients as compared to the controls (P<0.001). The frequency of GA genotype of TNF-β (+252A/G) was significantly higher in patients than in controls while the AA genotype was completely absent in OLP patients. These results indicated that allele A and genotype GA of TNF-α (-308G/A) as well as the GA genotype of TNF-β (+252A/G) polymorphisms are associated with OLP risk. The frequencies of alleles and genotypes of -1082G/A, -819C/T and -592C/A polymorphisms in IL-10 gene did not differ significantly between OLP patients and controls (P>0.05). However, haplotype ATA extracted from 1082G/A, -819C/T, -592C/A polymorphisms of IL-10 were more prevalent in OLP patients when compared to controls indicating its possible association with OLP susceptibility. Conclusion It is concluded that TNF-α (-308G/A), TNF-β (+252A/G) and IL-10 (-1082G/A, -819C/T and -592C/A) polymorphisms are associated with the susceptibility of OLP, thus giving additional support for the genetic basis of this disease.

Apolipoprotein E Gene Polymorphism and Serum Lipid Profile in Saudi Patients with Psoriasis

Background/Aim. Apolipoprotein E (APOE) gene variants have been reported to influence psoriasis risk. However, data is limited to a few ethnicities and no similar study has been performed in middle eastern populations. We investigated this association in Saudi psoriasis patients. Methods. Saudi subjects (294) were genotyped for APOE gene using APOE StripAssay kit. Results. The frequencies of alleles ε2, ε4, and genotypes ε3/ε4 and ε3/ε2 were significantly higher in psoriasis patients compared with those in controls. The frequency of ε3 allele and ε3/ε3 genotype was significantly lower in patients. Other genotypes, ε2/ε4, ε2/ε2, and ε4/ε4, were absent in both groups. The serum cholesterol, triglycerides, and LDL levels were significantly higher in psoriasis patients contrary to HDL level. Patients with APOE ε4 had significantly higher levels of total cholesterol and LDL cholesterol, whereas those with the ε2 had higher HDL cholesterol, and triglycerides. Conclusion. APOE alleles ε2, ε4, and genotypes ε2/ε3 and ε4/ε3 are associated with psoriasis and can be a risk factor while allele ε3 and genotype ε3/ε3 may be protective for psoriasis in Saudis. Results of lipid profile support that psoriasis is one of the independent risk factors for hyperlipidemia and emphasize the need of screening cardiovascular diseases in psoriatic patients.

HLA-DRB1 association with schizophrenia in Saudi Arabian patients

Abstract Objective. This study is aimed to examine the association between HLA-DRB1 alleles frequency and schizophrenia in Saudi Arabs. Methods. The DRB1 region of major histocompatibility complex was screened by polymerase chain reaction/sequence specific primers (PCR/SSP) in 180 schizophrenia patients and 200 matched controls. Results. The frequency of DRB1*03 was found to be significantly higher in schizophrenia patients as compared to controls, whereas a significantly lower frequency of DRB1*06 was observed in schizophrenia patients as compared to controls. Molecular sub-typing of the most prevalent allele DRB1*03 (30.56%) revealed the presence of DRB1*030101, *030102 alleles. Conclusion. The results of this study suggested a positive association between DRB1*03 (DRB1*030101, DRB1*030102) with schizophrenia and a negative association of DRB1*06 with schizophrenia in Saudi Arabs. However it is not clear whether the DRB1*03 alleles have a direct causal role in the etiology of schizophrenia or if they are in direct linkage disequilibrium with another true susceptibility locus. Since schizophrenia is a complex phenotype, it is expected that many factors might act together to produce the final outcome. Further studies are warranted involving larger population to confirm the observations reported in this study.

Genetic Variants of Interleukin-10 Gene Promoter are Associated with Schizophrenia in Saudi Patients: A Case-Control Study

Background: Interleukin-10 (IL-10) gene is considered as a potential candidate gene in schizophrenia association studies. The polymorphisms on IL-10 gene have been reported to be linked with susceptibility to the development of schizophrenia within consistent results. Aims: The aim of this case-control study was to examine whether the -1082A/G, -819T/C, and -592A/C polymorphisms in IL-10 gene are implicated in schizophrenia development in the Saudi population. Materials and Methods: Molecular genotyping of IL-10 gene polymorphisms was performed to analyze the genotypes and alleles distribution of three single-nucleotide polymorphisms (SNPs) in patients (n = 181) and healthy individuals as control group (n = 211). Results: The frequencies of GA genotype at -1082, and CC genotype at positions -592 and -819 were significantly higher in schizophrenia patients compared to healthy subjects suggesting that GA, CC, and CC genotypes are susceptible to schizophrenia. The ACC haplotype known to be associated with intermediate production of IL-10 are more prevalent in our schizophrenia patients. On the other hand, genotypes -1082 GG, -819 CT, and -592 CA of IL-10 were more prevalent in healthy controls suggesting protective effects of GA, CT, and CA genotypes against schizophrenia. There was no significant association of IL-10 polymorphisms with sex or positive or negative symptoms of schizophrenia. Conclusion: This study indicates that the IL-10 gene polymorphisms play a significant role in the etiology of schizophrenia in Saudi Arabians patients.

Tumor necrosis factor-α and -β genetic polymorphisms as a risk factor in Saudi patients with schizophrenia

Background Schizophrenia is one of the most common devastating psychiatric disorders that negatively affects the quality of life and psychosocial functions. Its etiology involves the interplay of complex polygenic influences and environmental risk factors. Inflammatory markers are well-known etiological factors for psychiatric disorders, including schizophrenia. Objective The aim of this study was to investigate the association of proinflammatory cytokine genes, tumor necrosis factor (TNF)-α (−308G/A) and TNF-β (+252A/G) polymorphisms with schizophrenia susceptibility. Subjects and methods TNF-α and TNF-β genes were amplified using amplification refractory mutation system primers in 180 schizophrenia patients and 200 healthy matched controls recruited from the Psychiatry Clinic of Prince Sultan Military Medical City, Riyadh. The frequencies of alleles and genotypes of TNF-α (−308G/A) and TNF-β (+252A/G) polymorphisms in patients were compared with those in controls. Results The frequencies of TNF-α (−308) allele A and genotype GA were significantly higher, while those of allele G and genotype GG were lower in schizophrenia patients as compared to controls, indicating that genotype GA and allele A of TNF-α (−308G/A) may increase susceptibility to schizophrenia, while genotype GG and allele G may reduce it. On the other hand, the distribution of alleles and genotypes of TNF-β (+252A/G) polymorphism does not differ significantly in patients from controls; however, the frequency of genotype GG of TNF-β (+252A/G) was significantly higher in male patients than in female patients. The distribution of TNF-α (−308G/A) and TNF-β (+252A/G) polymorphisms was almost similar in schizophrenia patients with negative or positive symptoms. Conclusion TNF-α (−308G/A) and TNF-β (+252G/A) polymorphisms may increase the susceptibility to schizophrenia in Saudi patients and could be a potential risk factor for its etiopathogenesis. However, further studies are warranted involving a larger sample size to strengthen our findings.

Apolipoprotein E Gene Polymorphisms in Saudi Patients with Systemic Lupus Erythematosus

Apolipoprotein E (APOE) is a glycosylated protein with multiple biological properties. APOE gene polymorphism plays a central role in lipid metabolism and has recently been suggested to regulate inflammation. Our objective is to evaluate whether APOE polymorphism affects susceptibility to SLE. APOE genotyping was performed using ApoE StripAssay™ kit. Results indicated significantly higher frequencies of allele ∊4 and genotype ∊3/∊4 and lower frequencies of allele ∊3 and genotype ∊3/∊3 in SLE patients than controls. APOE ∊2 allele was found in three patients, whereas it was absent in controls. The frequencies of allele ∊4 and genotype ∊3/∊4 were significantly higher in SLE patients with renal involvement and those of alleles ∊2, ∊4 and genotypes ∊2/∊3, ∊3/∊4 were higher in patients with neuropsychiatric symptoms. It is concluded that APOE allele ∊4 is associated with susceptibility risk/clinical manifestations of SLE and ∊2 may increase its severity while ∊3 is protective for SLE in Saudis.

Inflammation-related cytokine gene polymorphisms in Behçet's disease.

Behçet’s disease (BD) is a complex, multisystemic inflammatory disorder of unclear etiology. Single nucleotide polymorphisms in tumor necrosis factor (TNF) and interleukin (IL)-10 genes have been implicated in susceptibility to BD with inconsistent results in several ethnic populations. The aim of this case-control study was to evaluate the association of TNF-α (−308G/A), TNF-β (+252A/G), and IL-10 (−1082G/A, −819C/T, and −592 C/A) polymorphisms with susceptibility of BD in Saudi patients. Molecular genotyping of TNF-α, TNF-β, and IL-10 gene polymorphisms was performed to analyze the alleles and genotypes distribution in 272 Saudi subjects, including BD patients (61) and healthy controls (211). The frequencies of allele A and genotype GA of TNF-α (−308G/A) were significantly higher, whereas those of allele G and genotypes GG were significantly lower in BD patients than controls, indicating that A allele and GA genotype are susceptible, while G allele and GG genotype may be refractory to BD. The distribution of frequencies of alleles and genotype of TNF-β (+252A/G) promoter polymorphism was not significantly different between BD patients and healthy controls. Genotypes 1082GG, −819TT, and 592AA of IL-10 polymorphisms are significantly associated with susceptibility risk of BD, while genotypes 1082AA, 1082GA, 819CC, 819CT, 592CC, and 592CA are resistant to BD. This study indicates that TNF-α (−308G/A) and IL-10 (−1082G/A, −819C/T, and −592C/A) polymorphisms are associated with risk of BD susceptibility in Saudi patients. However, larger scale studies in Saudi population as well as in other ethnicities are needed to confirm this association.