title: BLK pathway-associated rs13277113 GA genotype is more frequent in SLE patients and associated with low gene expression and increased flares.
abstract: We aimed to evaluate the relationship between some important genetic variations and expressions of these genes in our SLE population. We also determined their association with clinical parameters. Eighty-four SLE patients (79 F, 5 M) and 105 healthy controls (98 F, 7 M) were included in the study. rs13277113, rs2736340, rs7829816, rs6983130, rs2613310, and rs704853 polymorphisms, gene expressions of Src family kinases (Blk, Hck, Lck, and Lyn), and Syk kinases (Syk, ZAP70) were studied by real-time PCR. The heterozygous genotypic pattern (GA) for rs13277113 polymorphism was more frequent in patients with SLE when compared to that in controls (48.8 vs. 31.4%, p = 0.035). Other genotype variants were similar in SLE patients and controls. In the SLE group, the heterozygous genotype for rs13277113 was significantly less frequent in active SLE patients (58.8 vs. 26.7%, p = 0.01). SLE flares according to the SELENA-SLEDAI flare index were significantly more frequent in GA (rs13277113) (70 vs. 37%) and CT (rs2736340) genotypes (66.7 vs. 35.2%) than those in other genotypes (p values <0.01). The relative expression of Blk gene was significantly decreased in the SLE group as compared to that in controls (0.52 times, 95%CI 0.19-0.85). The gene expressions of Blk and ZAP70 were significantly lower in SLE patients who had flares according to the SELENA-SLEDAI flare index when compared to those in others (p values 0.01 and 0.017). We observed more frequent heterozygous GA genotypic pattern (rs13277113) in our SLE patients compared to that in controls; and it was associated with disease flares. Blk gene expression in SLE was lower, especially in relapsing patients.
authors.affiliation: Department of Rheumatology, Trakya University Medical Faculty, Edirne, Turkey. omernpamuk@yahoo.com.|, Eski Yildiz Cad. Park Apt. No:22 Daire:18 Besiktas, 34349, Istanbul, Turkey. omernpamuk@yahoo.com.
authors.forename: Omer Nuri
authors.initials: ON
authors.lastname: Pamuk
authors.affiliation: Department of Medical Genetics, Trakya University Medical Faculty, Edirne, Turkey.
authors.forename: Hakan
authors.initials: H
authors.lastname: Gurkan
authors.affiliation: Department of Hematology, Trakya University Medical Faculty, Edirne, Turkey.
authors.forename: Gulsum Emel
authors.initials: GE
authors.lastname: Pamuk
authors.affiliation: Department of Medical Genetics, Trakya University Medical Faculty, Edirne, Turkey.
authors.forename: Hilmi
authors.initials: H
authors.lastname: Tozkır
authors.affiliation: Trakya University Health Services Vocational College, Edirne, Turkey.
authors.forename: Julide
authors.initials: J
authors.lastname: Duymaz
authors.affiliation: Department of Medical Genetics, Trakya University Medical Faculty, Edirne, Turkey.
authors.forename: Metin
authors.initials: M
authors.lastname: Yazar
mesh_terms: D000328:Adult; D017252:CD3 Complex / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D060888:Real-Time Polymerase Chain Reaction; D000072377:Syk Kinase / Q000235:genetics; D016896:Treatment Outcome; D014421:Turkey; D019061:src-Family Kinases / Q000235:genetics*
chemical_list: D017252:CD3 Complex; C121704:CD3 antigen, zeta chain; C584409:BLK protein, human; C000606896:SYK protein, human; D000072377:Syk Kinase; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases
keywords: Gene expression; Genetics; Polymorphism; Systemic lupus erythematosus