Association of Functional Polymorphism in Protein Tyrosine Phosphatase Nonreceptor 22 (PTPN22) Gene with Vitiligo.

The protein tyrosine phosphatase nonreceptor 22 (PTPN22) is associated with susceptibility to autoimmune diseases. The functional polymorphism in PTPN22 at 1857 is a strong risk factor for vitiligo susceptibility in Europeans; however, controversy exits in other populations. Present study was aimed to determine whether the PTPN22 C1857T polymorphism confers susceptibility to vitiligo in Saudi Arabians. Genomic DNA was extracted and amplified using tetra primer amplification-refractory mutation system polymerase chain reaction (ARMS-PCR) method. The frequencies of allele T and genotype CT of PTPN22 C1858T polymorphism were significantly higher, whereas those of allele C and genotype CC were lower in patients as compared with controls (P < 0.0001). The genotype TT was absent in both the patients and controls. It is concluded that PTPN22 C1858T polymorphism is strongly associated with vitiligo susceptibility. However, additional studies are warranted using large number of samples from different ethnicities and geographical areas.

Methylenetetrahydrofolate Reductase C677T Gene Polymorphism as Risk Factor for Psoriasis in Saudis.

Methylenetetrahydrofolate reductase (MTHFR) has been linked with the etiopathogenesis of psoriasis with inconsistent results. Methylenetetrahydrofolate reductase C677T polymorphism was evaluated in 106 Saudi psoriasis vulgaris patients and 280 matched healthy controls using PCR-RFLP (restriction fragment length plymorphism) technique. The cardiovascular risk factors were also compared in cases and controls. Allele T and genotypes CT and TT were found to be increased while allele C and genotype CC significantly decreased in psoriasis patients as compared with controls (P < .001). These results showed that the T-allele and T-containing genotypes (TT, CT) of MTHFR C677T are significantly linked with psoriasis susceptibility while C-allele and CC genotype are protective for it. Body mass index, fasting glucose, total cholesterol, low-density lipoprotein, triglycerides, and C-reactive protein, known markers for cardiovascular diseases, were found to be significantly elevated in the patient group as compared with the controls. It is concluded that the MTHFR C677T polymorphism increases psoriasis risk in Saudi patients.

Cytokine Gene Polymorphisms in Saudi Patients With Atopic Dermatitis: A Case-Control Study.

The cause of atopic dermatitis (AD) is multifactorial and a number of genes including cytokines have been involved. We genotyped 315 subjects for polymorphisms in TNF-α and TNF-ß and IL-10 genes. Patients had significantly higher frequency of GA genotype of TNF-α (-308 G/A) than healthy controls. Patients with AD and controls had similar distribution of A and G alleles. Genotype AA was found in 7.11% of controls while completely absent in cases. The frequencies of genotypes GG and AA of TNF-ß (+252 A/G) polymorphism were higher whereas the frequency of genotype GA was significantly lower in patients than the controls. The frequencies of genotypes GG and AA of IL-10 (1082 G/A) polymorphism were significantly increased whereas genotype GA was decreased in patients than the controls. It is concluded that TNF-α (-308 G/A), TNF-ß (+252 A/G), and IL-10 (-1082 G/A) polymorphisms are linked with the susceptibility of AD in Saudis and can be a risk factor.

The Protein Tyrosine Phosphatase Nonreceptor 22 (PTPN22) R620W Functional Polymorphism in Psoriasis.

BACKGROUND: Psoriasis is a complex autoimmune disease caused by the interaction of genetic and environmental factors. PTPN22 gene polymorphism has been reported to affect psoriasis susceptibility; however, no data are available for Middle Eastern populations. OBJECTIVE: The aim of this study was to investigate the association of PTPN22 (1858C/T) R620W polymorphism with psoriasis in a Saudi cohort. METHODS: Saudi subjects (n = 306) including patients with psoriasis (n = 106) and matched controls (n = 200) were studied for PTPN22 variants using tetra-primer amplification refractory mutation system-polymerase chain reaction method. The frequencies of alleles and genotypes of PTPN22 (1858C/T) polymorphism were compared between patients and controls. RESULTS: The frequency of CT genotype of PTPN22 (1858C/T) polymorphism was significantly higher, whereas that of CC genotype was lower in patients with psoriasis than in controls (P < .001, relative risk [RR] = 7.151). The homozygous genotype TT was absent in both the patients and healthy controls. The frequency of allele T encoding tryptophan (W) was significantly increased (P < .001, RR = 5.76), whereas that of allele C encoding arginine (R) decreased in psoriasis cases as compared with controls (P < .001, RR = 0.173) indicating that individuals carrying allele T are more susceptible to psoriasis than noncarriers. CONCLUSIONS: PTPN22 (1858C/T) polymorphism is positively associated with susceptibility of psoriasis in Saudis and can be developed as biomarker for evaluating psoriasis risk. However, further studies on PTPN22 polymorphism in larger samples from different geographical areas and ethnicity are warranted.

Tumor necrosis factor-α and -ß 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-ß (+252A/G) polymorphisms with schizophrenia susceptibility. SUBJECTS AND METHODS: TNF-α and TNF-ß 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-ß (+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-ß (+252A/G) polymorphism does not differ significantly in patients from controls; however, the frequency of genotype GG of TNF-ß (+252A/G) was significantly higher in male patients than in female patients. The distribution of TNF-α (-308G/A) and TNF-ß (+252A/G) polymorphisms was almost similar in schizophrenia patients with negative or positive symptoms. CONCLUSION: TNF-α (-308G/A) and TNF-ß (+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.

The SPARC-related modular calcium binding protein 2 (SMOC2) gene polymorphism in primary glaucoma: a case-control study.

Primary glaucomas are among the most common eye diseases that may potentially result in bilateral blindness. Both genetics and environmental factors are reported to be involved in the etiology of primary glaucomas. Secreted protein acidic and rich in cysteine (SPARC)-related modular calcium binding protein 2 (SMOC2) is a matricellular glycoprotein encoded by the SMOC2 gene and known to regulate the expression of extracellular matrix (ECM) proteins and matrix metalloproteinases (MMPs), which play an important role in the pathogenesis of primary glaucomas. The frequencies of alleles and genotypes of SMOC2 variants were examined in 406 Saudi subjects, including primary open angle glaucoma (POAG, n=140) and primary angle closure glaucoma (PACG, n=64) patients and 202 matched healthy controls using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Genotyping of SMOC2 polymorphism (rs13208776) revealed a significantly higher frequency of the heterozygous genotype GA (P<0.01) and a lower frequency of wild type GG genotype (P=0.05) in glaucoma patients compared to the controls. Upon stratification of the patients on the basis of types of glaucoma, PACG patients had a significantly higher frequency of GA genotype as compared to the controls (P<0.01), whereas there was no significant difference between the POAG patient and control groups in frequencies of SMOC2 alleles and genotypes. Further, there was no significant difference in frequency distribution of alleles and genotypes between male and female patients. This study indicates that the GA genotype of SMOC2 (G>A) polymorphism is significantly associated with PACG and may be a risk factor. However, further large-scale studies in the Saudi population as well as in other ethnic populations are needed to confirm this association.

Association of the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism with primary glaucoma in Saudi population.

BACKGROUND: Methylenetetrahydrofolate reductase (MTHFR), a critical enzyme in folate metabolism is involved in DNA synthesis, DNA repair and DNA methylation. The functional polymorphism of MTHFR gene, C677T has been shown to impact various diseases and implicated as a risk factor for the development of various neurodegenerative disorders including glaucoma. METHODS: We investigated MTHFR C677T genotypes and alleles frequencies in primary glaucoma [primary open angle glaucoma (POAG) and primary angle closure glaucoma (PACG)] patients and matched healthy controls in a case-control study. Two hundred ten primary glaucoma cases were studied for MTHFR C677T polymorphism and compared with 280 controls taken from the healthy population, employing the polymerase chain reaction-restriction fragment length polymorphism technique (PCR-RFLP). The MTHFR gene was amplified using specific primers. The PCR products (294 bp) was subsequently digested with HinfI (New England Biolabs) at 37 °C for 12 h, separated by electrophoresis on 2 % agarose gels, and visualized with ethidium bromide staining. The restriction digestion yielded 168 and 126 bp fragments for TT, 294, 168 and 126 bp fragments for CT and undigested PCR product 294 bp indicating CC genotype. RESULTS: We found the frequency of the genotypes and alleles of MTHFR C677T differ significantly between cases and controls. The frequencies of allele T and genotype CT were significantly higher while the frequencies of allele C and genotype CC were lower in primary glaucoma patients as compared to controls (p <0.05). Upon stratification of our results into POAG and PACG, significantly higher frequencies of allele T (19.44 %) and genotype CT (38.89 %) were found in POAG patients compared to controls (12.5 % and 25 % respectively). The frequencies of alleles and genotypes were almost similar in PACG and controls (p = 0.8). CONCLUSION: This study indicates that the allele T and genotype CT of MTHFR C677T polymorphism are significantly associated with POAG while allele C and CC genotype may be protective for it. We conclude that the MTHFR C677T polymorphism increases the risk for POAG development in Saudi population and can be a genetic marker however, further studies are needed with multiple-ethnic populations affected with POAG to strengthen these findings.

Genetic Association of HLA-A*26, -A*31, and -B*51 with Behcet's Disease in Saudi Patients.

BACKGROUND: HLA-B*51 has been universally associated with Behcet's disease (BD) susceptibility, while different alleles of HLA-A have also been identified as independent BD susceptibility loci in various ethnic populations. The objective of this study was to investigate associations of HLA-A and -B alleles with BD in Saudi patients. MATERIALS AND METHODS: Genotyping for HLA-A and HLA-B was performed using HLA genotyping kit (Lab type((R)) SSO) in 120 Saudi subjects, including 60 BD patients and 60 matched healthy controls. RESULTS: Our results revealed that frequencies of HLA-A*26, -A*31, and -B*51 were significantly higher in BD patients than in controls, suggesting that HLA-A*26, -A*31, and -B*51 are associated with BD. The frequency of HLA-B*15 was significantly lower in BD patients than in controls. Stratification of genotyping results into active and nonactive forms of BD revealed that the frequency of HLA-A*31 was significantly higher in the nonactive form than in the active form of BD, while there was no significant difference in the distribution of other alleles between the two forms of BD. CONCLUSION: This study suggests that HLA-A*26, -A*31, and -B*51 are associated with susceptibility risk to BD, while HLA-B*15 may be protective in Saudi patients. However, larger scale studies are needed to confirm these findings.

Association of genetic polymorphisms in interferon-γ, interleukin-6 and transforming growth factor-ß1 gene with oral lichen planus susceptibility.

BACKGROUND: Oral lichen planus (OLP) is a premalignant mucocutaneous disease in which genetic factors and immune responses play a major role. Cytokines play an important role in the pathogenesis and disease progression of OLP. The aim of this study was to investigate the impact of gene polymorphisms of T helper cell subtype Th1 and Th2 cytokines, interferon-gamma (IFN-γ), interleukin-6 (IL-6) and transforming growth factor (TGF)-ß1 on OLP susceptibility in a Saudi cohort. METHODS: Forty two unrelated patients with OLP and 195 healthy controls were genotyped for IFN-γ (874A/T), IL-6 (174G/C) and TGF-ß1 (509C/T) polymorphisms. RESULTS: The frequency of genotype AT of IFN-γ (874A/T) was significantly higher while genotype AA was lower in OLP patients as compared to controls (P < 0.05). The frequency of T containing genotypes (AT + TT) was also higher in OLP patients as compared to that in controls (P = 0.003). The frequencies of allele T was higher while that of allele A lower in patients than the controls however the difference was not statistically significant (P = 0.07). There was no significant difference in the frequencies of alleles and genotypes of IL-6 (174G/C) and TGF-ß1 (509C/T) polymorphisms between patient and control groups. These results indicated that genotype AT of IFN-γ (874A/T) polymorphism is associated with OLP risk and genotype AA is protective to OLP. On the other hand the polymorphisms IL-6 (174G/C) and TGF-ß1 (509C/T) may not be associated with OLP risk in our population. CONCLUSION: It is concluded that IFN-γ (874A/T) polymorphism is associated with the susceptibility of OLP, however further studies with large sample size involving different ethnic populations should be conducted to strengthen our results.

Association of tumor necrosis factor-α and -ß gene polymorphisms in inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a complex, multifactorial, chronic inflammatory disorder of the gastrointestinal tract in which immune dysregulation caused by genetic and/or environmental factors plays an important role. The aim of this case-control study was to evaluate the association of tumor necrosis factor-alpha (TNF-α) (308) and -ß (+252) polymorphisms with susceptibility of IBD. A total of 379 Saudi subjects including 179 IBD patients (ulcerative colitis (UC) =84 and Crohn's disease (CD) =95) and 200 age- and sex-matched healthy controls were recruited. TNF-α and TNF-ß genes were amplified using an amplification refractory mutation systems polymerase chain reaction methodology to detect TNF-α (-308) and -ß (+252) polymorphisms. The frequency of the GA genotype of TNF-α (-308G/A) was higher, and the frequencies of the GG and AA genotypes were significantly lower in IBD patients compared with those in controls, indicating that genotype GA-positive individuals are susceptible to IBD and that the GG and AA genotypes exert a protective effect. The frequency of allele A of TNF-α (-308G/A) was significantly higher and that of allele G was lower in IBD patients compared with those in controls, indicating an association of allele A with IBD risk in Saudi patients. On stratification of IBD patients into UC and CD, an almost similar pattern was noticed in both the groups. The results of TNF-ß (+252A/G) polymorphisms showed a significant increase in the frequency of the GG genotype in IBD patients, suggesting a positive association of GG genotype with IBD risk. On stratification of IBD patients into UC and CD, the genotype GG of TNF-ß was associated with susceptibility risk to UC but not CD. The frequencies of alleles and genotypes of both TNF-α and-ß polymorphisms are not affected by sex or type of IBD (familial or sporadic). TNF-α (-308G/A) and TNF-ß (+252A/G) polymorphisms are associated with risk of developing IBD in Saudi population.

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 ε4 and genotype ε3/ε4 and lower frequencies of allele ε3 and genotype ε3/ε3 in SLE patients than controls. APOE ε2 allele was found in three patients, whereas it was absent in controls. The frequencies of allele ε4 and genotype ε3/ε4 were significantly higher in SLE patients with renal involvement and those of alleles ε2, ε4 and genotypes ε2/ε3, ε3/ε4 were higher in patients with neuropsychiatric symptoms. It is concluded that APOE allele ε4 is associated with susceptibility risk/clinical manifestations of SLE and ε2 may increase its severity while ε3 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-ß (+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-ß, 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-ß (+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.

Apolipoprotein E polymorphism is associated with susceptibility to schizophrenia among Saudis.

INTRODUCTION: Apolipoprotein E (APOE) genotypes influence the phenotype of several neurodegenerative disorders including Alzheimer's and Parkinson disease and may affect schizophrenia pathogenesis. This study was undertaken to determine the association between APOE gene polymorphisms and schizophrenia in the Saudi population. MATERIAL AND METHODS: APOE allele and genotype frequencies were studied in 380 Saudi subjects including schizophrenia patients and matched controls using polymerase chain reaction (PCR) and reverse-hybridization techniques. RESULTS: The frequencies of the APOE allele ε2 and genotypes ε2/ε3 and ε2/ε4 were significantly higher in the schizophrenia patients as compared to controls, suggesting that the ε2 allele and its heterozygous genotypes may increase the susceptibility to schizophrenia. In contrast, the frequencies of the ε3 allele and ε3/ε3 genotype were lower in patients as compared to controls, suggesting a protective effect of APOE ε3 for schizophrenia. This study indicated that APOE ε4 was differentially associated with schizophrenia depending on the symptoms as the frequency of the ε4 allele was significantly higher in schizophrenia patients with positive symptoms. By contrast, no significant association between APOE ε4 and schizophrenia patients with negative symptoms was observed. Genotypes ε2/ε2 and ε4/ε4 were absent in patients and controls. Moreover, the age of onset was significantly lower in patients with the APOE ε2/ε3 genotype. There was no significant difference in the frequencies of APOE alleles and genotypes between male and female schizophrenia patients. CONCLUSIONS: The results of this study clearly show that APOE alleles and genotypes are associated with risk of developing schizophrenia and early age of onset in Saudis.

TNF-α, TNF-ß 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-ß 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-ß (+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-ß (+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-ß (+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-ß (+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.

TNF-α, TNF-ß 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. .

Prevalence of ocular pseudoexfoliation syndrome and associated complications in Riyadh, Saudi Arabia.

OBJECTIVES: To assess the prevalence of pseudoexfoliation syndrome (PEX), and associated ophthalmic complications among Saudi patients. METHODS: The prevalence of PEX and associated ocular co-morbidities were determined among the Saudi patients visiting the Primary Care Clinic of Prince Sultan Military Medical City, Riyadh, Kingdom of Saudi Arabia, between January 2009 and January 2010. A total of 1967 patients were examined biomicoscopically by ophthalmologists to determine the presence of PEX and associated ocular complications. RESULTS: Sixty-nine of the 1967 examined patients (3.5%) showed the presence of PEX with no significant gender difference. There was an age dependent increase in the prevalence of PEX after the age of 50 years. Pseudoexfoliation syndrome was associated with higher intraocular pressure, cataract, and poor vision. There was no significant difference in the prevalence of PEX in male and female Saudi patients. CONCLUSION: Pseudoexfoliation syndrome is an age-related disorder, and its prevalence increases with age. Further larger population based studies are warranted to assess the prevalence of PEX and associated risk factors. 

Genetic association of apolipoprotein E polymorphisms with inflammatory bowel disease.

AIM: To study the association of apolipoprotein E (APOE) polymorphisms with the susceptibility of inflammatory bowel disease (IBD) in Saudi patients. METHODS: APOE genotyping was performed to evaluate the allele and genotype frequencies in 378 Saudi subjects including IBD patients with ulcerative colitis (n = 84) or Crohn's disease (n = 94) and matched controls (n = 200) using polymerase chain reaction and reverse-hybridization techniques. RESULTS: The frequencies of the APOE ε2 allele and ε2/ε3 and ε2/ε4 genotypes were significantly higher in IBD patients than in controls (P < 0.05), suggesting that the ε2 allele and its heterozygous genotypes may increase the susceptibility to IBD. On the contrary, the frequencies of the ε3 allele and ε3/ε3 genotype were lower in IBD patients as compared to controls, suggesting a protective effect of APOE ε3 for IBD. The prevalence of the ε4 allele was also higher in the patient group compared to controls, suggesting that the ε4 allele may also increase the risk of IBD. Our results also indicated that the APOE ε4 allele was associated with an early age of IBD onset. No effect of gender or type of IBD (familial or sporadic) on the frequency distribution of APOE alleles and genotypes was noticed in this study. CONCLUSION: APOE polymorphism is associated with risk of developing IBD and early age of onset in Saudi patients, though further studies with a large-size population are warranted.

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.

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 ε 4 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.

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.