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BACKGROUND: The risk of developing immune tolerance to self-antigens in autoimmune thyroiditis is largely associated with a mutation in the CTLA-4 gene, the product of which negatively regulates T-cell activity. AIM: To study the A49G (rs231775) CTLA-4 polymorphism in patients with autoimmune thyroiditis in a sample of Azerbaijani residents and the effect of the frequency of identified alleles and genotypes on the level of antibodies to thyroid peroxidase and thyroglobulin. MATERIAL AND METHODS: A study was conducted in 2021–2023 involving 170 patients with autoimmune thyroiditis and 65 individuals without thyroid pathology or other autoimmune diseases, who formed a comparison group. The groups were matched by gender and age. Based on the patient history, thyroid status study results, thyroid ultrasound data, and organ-specific antibody assessment, the patients were diagnosed with autoimmune thyroiditis. The routine thyroid status study results in the comparison group were within normal limits. Genotyping of the A49G (rs231775) polymorphism was performed using polymerase chain reaction followed by digestion of the reaction product with PspEI restriction endonuclease. The results of the quantitative studies were presented as the median (Me) and interquartile range (25th quartile; 75th quartile). The correspondence of genotype frequencies to the Hardy–Weinberg equilibrium was assessed using the χ2 criterion. RESULTS: The results revealed a statistically significant increase in the frequency of the G allele (48%) compared to the control group [33.8%; p=0.039, χ2=4.27, odds ratio (OR) 1.865, 95% confidence interval (CI) 1.028–3.382] and a decrease in the frequency of the A allele (51.2%) relative to the control group (66.1%; p=0.0389, χ2=4.27, OR=0.536, CI=0.296–0.973). In 22.4% of patients with the GG genotype (p=0.005, χ2=7.86, OR=0.237, 95% CI=0.088–0.635) and 55.6% of patients with the G allele (p=0.0012, χ2=10.43, OR=0.360, 95%, CI=0.192–0.674), thyroglobulin antibody titers were more than 100 IU/ml. Thyroid peroxidase antibody levels of 100 IU/ml or more were recorded in 22.7% of study participants with the GG genotype (p=0.030) and 50.0% with the G allele (p=0.048). CONCLUSION: Elevated titers of antibodies to thyroid peroxidase and thyroglobulin were detected in patients from the population of Azerbaijan with the G allele and homozygous genotype GG of the +49A/G polymorphism of the CTLA-4 gene.
BACKGROUND: The risk of developing immune tolerance to self-antigens in autoimmune thyroiditis is largely associated with a mutation in the CTLA-4 gene, the product of which negatively regulates T-cell activity. AIM: To study the A49G (rs231775) CTLA-4 polymorphism in patients with autoimmune thyroiditis in a sample of Azerbaijani residents and the effect of the frequency of identified alleles and genotypes on the level of antibodies to thyroid peroxidase and thyroglobulin. MATERIAL AND METHODS: A study was conducted in 2021–2023 involving 170 patients with autoimmune thyroiditis and 65 individuals without thyroid pathology or other autoimmune diseases, who formed a comparison group. The groups were matched by gender and age. Based on the patient history, thyroid status study results, thyroid ultrasound data, and organ-specific antibody assessment, the patients were diagnosed with autoimmune thyroiditis. The routine thyroid status study results in the comparison group were within normal limits. Genotyping of the A49G (rs231775) polymorphism was performed using polymerase chain reaction followed by digestion of the reaction product with PspEI restriction endonuclease. The results of the quantitative studies were presented as the median (Me) and interquartile range (25th quartile; 75th quartile). The correspondence of genotype frequencies to the Hardy–Weinberg equilibrium was assessed using the χ2 criterion. RESULTS: The results revealed a statistically significant increase in the frequency of the G allele (48%) compared to the control group [33.8%; p=0.039, χ2=4.27, odds ratio (OR) 1.865, 95% confidence interval (CI) 1.028–3.382] and a decrease in the frequency of the A allele (51.2%) relative to the control group (66.1%; p=0.0389, χ2=4.27, OR=0.536, CI=0.296–0.973). In 22.4% of patients with the GG genotype (p=0.005, χ2=7.86, OR=0.237, 95% CI=0.088–0.635) and 55.6% of patients with the G allele (p=0.0012, χ2=10.43, OR=0.360, 95%, CI=0.192–0.674), thyroglobulin antibody titers were more than 100 IU/ml. Thyroid peroxidase antibody levels of 100 IU/ml or more were recorded in 22.7% of study participants with the GG genotype (p=0.030) and 50.0% with the G allele (p=0.048). CONCLUSION: Elevated titers of antibodies to thyroid peroxidase and thyroglobulin were detected in patients from the population of Azerbaijan with the G allele and homozygous genotype GG of the +49A/G polymorphism of the CTLA-4 gene.
Məqalədə süd vəzisi xərçənginin (SVX) erkən diaqnostikasında serum matriksmetalloproteinaza-7 (MMP7), MMP-9 və sisteinlə zəngin angiogen induktor 61-in (CYR61) rolunun araşdırılmasını əks etdirən tədqiqat işi haqqında məlumat verilir. Tədqiqata 2023-2024-cü illərdə Milli Onkoloji Mərkəzə müraciət etmiş və SVX diaqnozu qoyulmuş 30-51 yaşlı 74 qadının nəticələri daxil edilmişdir. Kontrol qrupunu 25-38 yaşlı praktik sağlam 15 qadının nəticələri təşkil etmişdir. Histokimyəvi analiz üsulları ilə SVX-nin biotipləri aydınlaşdırılmış, nəticələrə əsasən 8 qadında “tripl neqativ” və ya üçlü neqativ fenotipli, 33 qadında Her2 sekresiyası müsbət və 33 qadında isə Her2 sekresiyası mənfi olan SVX aşkar edilmişdir. Kontrol qrupun nəticələri həm SVX olan bütün qadınların nəticələri ilə, həm də biotiplərə uyğun olaraq müxtəlif yarımqrupların göstəriciləri ilə müqayisə edilmişdir. Tədqiqatın nəticələrinə əsasən, Her2-müsbət, Her2-mənfi və üçlü neqativ SVX yarımqrupları arasında bu göstəricilərdə statistik əhəmiyyətli fərq aşkar edilməmişdir. MMP-9-un səviyyəsində isə ümumi SVX qrupu ilə kontrol qrupu arasında statistik əhəmiyyətli fərq müşahidə edilmişdir (p<0,001). Tədqiqat göstərmişdir ki, Her2 sekresiyasından asılı olaraq SVX biotipləri arasında serum biomarkerlərinin səviyyəsində əsaslı fərq müəyyən edilmir. Ancaq serum MMP-9 və CYR-61 səviyyəsi SVX-nin biotipindən asılı olmayaraq SVX diaqnostikasında əhəmiyyətliLaborator biomarker kimi istifadə edilə bilər. В статье представлены результаты исследование, проведенного с целью выяснения диагностического значения уровней матричной металлопротеиназы-7 (MMP-7), MMP-9 и цистеин-40 содержащего ангиогенного индуктора 61 (CYR61) при раке молочной железы (РМЖ). В исследование были включены результаты 74 женщин в возрасте от 30 до 51 года, обратившихся в Национальный Онкологический Центр в 2023-2024 годах и с диагнозом РМЖ. Контрольную группу составили результаты 15 практически здоровых женщин в возрасте 25-38 лет. Биотипы РМЖ были определены с использованием гистохимических методов анализа; по результатам у 8 женщин был выявлен “тройной негативный” фенотип, у 33 женщин наблюдалась гиперсекреция Her2, и у 33 женщин секреция Her2 была отрицательной. Результаты контрольной группы были сопоставлены как с результатами всех женщин с РМЖ, так и с показателями различных подгрупп, разделенных по биотипам. По результатам исследования, статистически значимых различий в уровнях исследуемых показателей между подгруппами Her2-позитивного, Her2-негативного и тройного негативного РМЖ не выявлено. Однако статистически значимая разница была установлена между общей группой РМЖ и контрольной группой по уровню MMP-9 (p<0,001). Исследование показало, что существенных различий в уровнях сывороточных биомаркеров между биотипами РМЖ в зависимости от секреции Her2 не обнаружено. Тем не менее, уровень сывороточного MMP-9 и CYR-61 может использоваться в качестве значимого лабораторного биомаркера для диагностики РМЖ вне зависимости от биотипа. The article presents a study investigating the role of serum matrix metalloproteinase-7 (MMP7), MMP-9, and cysteine-rich angiogenic inducer 61 (CYR61) in the early diagnosis of breast cancer (BC). The study included results from 74 women aged 30-51 years who visited the National Oncology Centre in 2023-2024 and were diagnosed with BC. The control group consisted of results from 15 healthy women aged 25-38 years. The biotypes of BC were determined using histochemical analysis methods; results showed that 8 women had a 'triple-negative' phenotype, 33 women had Her2-positive hypersecretion, and 33 women had Her2-negative BC. The control group results were compared with both the overall results of all women with BC and the indicators of various subgroups according to biotypes. According to the study results, no statistically significant differences were found in the levels of the studied biomarkers among Her2-positive, Her2-negative, and triple-negative BC subgroups. However, a statistically significant difference was identified in MMP-9 and CYR-61 levels between the overall BC group and the control group (p<0.001). The study demonstrated that there are no significant differences in serum biomarker levels between BC biotypes depending on Her2 secretion. However, the serum MMP-9 level can be used as a significant laboratory biomarker for the diagnosis of BC, regardless of biotype.
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