scholarly journals Association of ANKK1 polymorphism with schizophrenia: negative findings from a genetic approach

Author(s):  
О.Ю. Федоренко ◽  
Д.З. Падерина ◽  
И.В. Пожидаев ◽  
А.С. Бойко ◽  
Е.Г. Корнетова ◽  
...  

Введение. Шизофрения - тяжелое мультифакториальное психическое расстройство, патогенез которого связан с нарушением функционирования дофаминергической нейротрансмиссии. Ген белка 1, содержащего анкириновый повтор и киназный домен (ANKK1, ankyrin repeat and kinase domain containing 1), тесно связан с функционированием гена дофаминового рецептора типа D2 (DRD2). Полиморфный вариант гена ANKK1 rs2734849 модулирует плотность экспрессии рецепторов дофамина DRD2 посредством регуляции фактора транскрипции NF-κB. В данной работе исследована ассоциация функционального полиморфного варианта rs2734849 гена ANKK1 с шизофренией. Методы. Обследовано 468 русских больных шизофренией (235 женщин/233 мужчины) и 126 здоровых лиц (62 женщины/44 мужчины) из Сибирского региона. Полиморфизм ANKK1 rs2734849 определяли методом ПЦР в реальном времени на приборе «Step One Plus» с использованием набора реагентов «TaqMan SNPGenotyping Assay» (Applied Biosystems, США). Статистическая обработка результатов генотипирования проводилась с использованием пакета программ SPSS для Windows, версия 21.0. Частоты генотипов и аллелей сравнивали между группами пациентов с шизофренией и здоровых лиц, используя тест χ2 Фишера. Результаты. Средний возраст больных шизофренией в общей группе составил 42,1 ± 12,4 года, в группе мужчин, больных шизофренией, 37,8 ± 11, лет, в группе женщин, больных шизофренией, 45,2 ± 13,9 лет. Продолжительность заболевания в общей группе (Me; 25%Q-75%Q) составила 13 (6; 22), в группе мужчин, больных шизофренией, 11, (5; 18), в группе женщин, больных шизофренией, 15 (7; 26). Результаты по частотам аллелей ANKK1 rs2734849, полученные для контрольной группы в нашем исследовании (rs2734849 MAF 45%), сопоставимы с данными для европеоидов (MAF 50%), приведенными в проекте «1000 геномов». Частоты генотипов (р = 0,37) и аллелей (р = 0,73) полиморфного варианта гена ANKK1 rs2734849 не различалась в группах больных шизофренией и здоровых лиц. Сравнение распределения генотипов и аллелей ANKK1 rs2734849 в группах мужчин и женщин, больных шизофренией, а также сопоставление этих групп с соответствующим по полу контролем не выявило статистически значимых различий. Возможно, это связано с недостаточным размером группы здоровых доноров. Не исключено, что это обусловлено сложной природой патофизиологических процессов, лежащих в основе шизофрении. Выводы. Функциональный полиморфизм ANKK1 rs2734849 не ассоциирован с шизофренией в выборке русских Сибирского региона. Objective. Schizophrenia is a severe highly heritable mental disorder. Genetic polymorphisms of dopaminergic pathways are related to pathogenesis of schizophrenia. Ankyrin Repeat and Kinase Domain containing 1 (ANKK1) gene is closely related to Dopamine Receptor D2 type (DRD2) gene functioning. Variants of ANKK1, specifically rs2734849, may function to affect DRD2 expression and density via regulating the transcription factor NF-κB. We examined whether the functional polymorphism ANKK1 rs2734849 is associated with schizophrenia. Methods. We recruited 468 patients with schizophrenia (235 women / 233 men) and 126 healthy individuals (62 women / 44 men) in Russian population of Siberian region. The polymorphism rs2734849 in the ANKK1 gene was genotyped with “Step One Plus”, using the kit “TaqMan SNPGenotyping Assay” (Applied Biosystems, USA). Statistical analysis was carried out using the SPSS software package for Windows, version 21.0. Genotype and allele frequencies were compared between groups of schizophrenia patients and healthy controls using the χ2 , Fisher tests. Results. The average age of patients with schizophrenia in the general group was 42.1 ± 12.4 years, in the group of men with schizophrenia - 37.8 ± 11.9 years, in the group of women with schizophrenia - 45.2 ± 13.9 years. The duration of the disease in the general group was 13 (6; 22), in the group of men with schizophrenia 11 (5; 18), in the group of women with schizophrenia 15 (7; 26), Me values were indicated (25% Q - 75% Q). The results on the allele frequencies of ANKK1 rs2734849 obtained for the control group in our study (rs2734849 MAF 45%) are comparable with the data for Europeoids (MAF 50%) presented in the 1000 Genomes project. The frequency of genotypes (р=0.37) and alleles (р=0.73) of the polymorphic variant ANKK1 rs2734849 in patients with schizophrenia did not differ from those in control subjects. Comparison of the ANKK1 rs2734849 genotypes and alleles distribution in the groups of men and women with schizophrenia, as well as a comparison of these groups with the corresponding by sex control persons, did not reveal statistically significant differences. Perhaps this is due to the insufficient size of the group of healthy controls. It is possible due to the complex nature of the pathophysiological processes underlying schizophrenia. Conclusion. The functional polymorphism rs2734849 in the ANKK1 gene was not associated with schizophrenia in Russian population of Siberian region.

2013 ◽  
Vol 28 (3) ◽  
pp. 274-279 ◽  
Author(s):  
Geom Seog Seo ◽  
Ji-In Yu ◽  
Soo-Cheon Chae ◽  
Won Cheol Park ◽  
Sae Ron Shin ◽  
...  

Background Our previous work indicated that, first, the embryonic ectoderm development (EED) gene is a candidate gene associated with the pathogenesis of ulcerative colitis (UC) and, second, that the haplotypes of the EED polymorphism are one of the markers for UC susceptibility. The risk of developing colorectal cancer (CRC) increases in patients with inflammatory bowel disease. Aim The present study aimed at determining the association between polymorphisms in the EED gene and CRC. Methods Genotype analysis of EED single nucleotide polymorphisms (SNPs) was performed with high-resolution melting analysis, and the genotype and allele frequencies of the EED SNPs were compared between CRC patients and healthy controls. The haplotype frequencies of EED for multiple loci were estimated using the expectation maximization (EM) algorithm. Results Our study had a power of 76.6% at a 0.05 significance level. Genotype and allele frequencies of the SNPs and haplotype frequencies of the EED gene in CRC patients were not significantly different from those in healthy controls. Only the allele frequency of g.-1850G>C in the rectal cancer (RC) patient group was significantly different from that of the control group (p=0.04). Similarly, the genotype and allelic frequencies of the EED SNPs for either tumor site (left or right) or tumor stage were not significantly different from those in healthy controls. However, our data show an association between the g.-993G>C polymorphism in the EED gene and the presence of lymph node metastasis in CRC. Conclusions These results suggest that the SNPs of the EED gene might not be associated with susceptibility to CRC. However, this study shows that the allele frequency of g.-1850G>C in the RC patient group was significantly different from that in the control group (p=0.04) and that g.-993G>C may play a role in the lymph node metastatic process of CRC.


2015 ◽  
Vol 40 (5) ◽  
Author(s):  
Havva Yıldız Seçkin ◽  
Göknur Kalkan ◽  
İsmail Benli ◽  
İlknur Bütün ◽  
Yalçın Baş ◽  
...  

AbstractObjective: Vitiligo is a chronic autoimmune depigmentation disease, which is characterized by loss of function of the melanocytes in epidermis. Recent studies suggest that oxidant/antioxidant status plays important role in the pathogenesis of vitiligo. We aimed to investigate possible associations between vitiligo and PON1 M / L55 and PON Q192R gene polymorphisms in the Turkish community.Methods: The 57 patients with vitiligo and 69 healthy controls were enrolled into the study. Genotyping was performed to identify PON1 M / L55 and PON Q192R gene polymorphism. Genotype and allele frequencies were compared between patients with vitiligo and healthy control group.Results: In patients (p=0.0061) and healthy controls (p=0.550), there was no significant statistical difference between L55M and Q192R polymorphisms of the PON1 gene. However, when L55M polymorphism was compared to MM homozygous genotype and LL+LM genotypes, it was notably higher in controls than in patients, which seems to be protective against the disease (p=0.034, OR:0. 3, 95% CU: 0.08-0.93). Although, there was no not a statistical difference in allele frequencies of Q192R polymorphism between patients and controls (p=0.242), the M allele of L55M polymorphism was significantly higher in controls than in patients with vitiligo, which means that it might be protective against vitiligo (p=0.009, OR: 0.48, 95% CI: 0.27-0.84).Conclusion: Even though there were no differences between patients and controls, this is the first study that investigated the possible associations between the PON1 M/L55 and PON Q192R gene polymorphisms within the Turkish population.


1997 ◽  
Vol 77 (02) ◽  
pp. 248-251 ◽  
Author(s):  
Lena Norlund ◽  
Johan Holm ◽  
Bengt Zöller ◽  
Ann-Kristin Öhlin

SummaryEndothelial dysfunction and haemostatic imbalance are believed to be important aetiological factors in the development of acute coronary syndromes. Thrombomodulin (TM) is an integral membrane protein crucial for normal endothelial function and activation of the protein C anticoagulant pathway. We have investigated the importance of a common C/T dimorphism in the TM gene (nucleotide 1418) for development of premature myocardial infarction (MI). The C/T dimorphism predicts an Ala455 to Val replacement in the sixth EGF-like domain of TM. The dimorphism was investigated in 97 MI survivors and 159 healthy controls. The C allele was significantly more frequent among patients than controls (p = 0.035). The allele frequency for the C allele was 0.82 in the patients and 0.72 in the control group. The plasma concentration of TM was investigated among healthy controls but was not related to the C/T dimorphism. In conclusion, the association of the C allele with premature MI, suggests that the TM gene and the C/T dimorphism may be aetiological factors involved in the pathogenesis of MI. Possibly, the Ala455 to Val replacement may affect the function of the TM molecule and the activation of the protein C anticoagulant pathway.


Author(s):  
Evgeniy Evdoshenko ◽  
Kristina Laskova ◽  
Maria Shumilina ◽  
Ekaterina Nekrashevich ◽  
Maria Andreeva ◽  
...  

Abstract Objective: Cognitive dysfunction is common in multiple sclerosis (MS). The Brief International Cognitive Assessment for MS (BICAMS) battery of tests has been suggested as a measure for the evaluation of the cognitive status of MS patients. This study aims to validate the BICAMS battery in the Russian population of MS patients. Methods: Age- and sex-matched MS patients (n = 98) and healthy individuals (n = 86) were included in the study. Symbol Digit Modalities Test (SDMT), California Verbal Learning Test, 2nd edition (CVLT-II) and the Brief Visuospatial Memory Test – Revised (BVMT-R) were administered to all participants. The battery was readministered 1 month later to 44 MS patients to investigate the test–retest reliability. Results: MS patients exhibited a significantly lower performance in testing with BICAMS than the control group in all three neuropsychological tests. Test–retest reliability was good for SDMT and CVLT-II (r = .82 and r = .85, respectively) and adequate for BVMT-R (r = .70). Based on the proposed criterion for impairment as z score below 1.5 SD the mean of the control group, we found that 34/98 (35%) of MS patients were found impaired at least in one cognitive domain. Patients with Expanded Disability Status Scale score ≥3.5 performed significantly worse than controls (SDMT, p < .0001; CVLT–II, p = .03; BVMT-R, p = .0004), while those with ≤3.0 scores did not. Conclusion: This study demonstrates that the BICAMS battery is a valid instrument to identify cognitive impairment in MS patients and it can be recommended for routine use in the Russian Federation.


Author(s):  
Frank Faltraco ◽  
Denise Palm ◽  
Adriana Uzoni ◽  
Lena Borchert ◽  
Frederick Simon ◽  
...  

AbstractA link between dopamine levels, circadian gene expression, and attention deficit hyperactivity disorder (ADHD) has already been demonstrated. The aim of this study was to investigate the extent of these relationships by measuring circadian gene expression in primary human-derived dermal fibroblast cultures (HDF) after dopamine exposure. We analyzed circadian preference, behavioral circadian and sleep parameters as well as the circadian gene expression in a cohort of healthy controls and participants with ADHD. Circadian preference was evaluated with German Morningness-Eveningness-Questionnaire (D-MEQ) and rhythms of sleep/wake behavior were assessed via actigraphy. After ex vivo exposure to different dopamine concentrations in human dermal fibroblast (HDF) cultures, the rhythmicity of circadian gene expression (Clock, Bmal1, Per1-3, Cry1) was analyzed via qRT-PCR. We found no statistical significant effect in the actigraphy of both groups (healthy controls, ADHD group) for mid-sleep on weekend days, mid-sleep on weekdays, social jetlag, wake after sleep onset, and total number of wake bouts. D-MEQ scores indicated that healthy controls had no evening preference, whereas subjects with ADHD displayed both definitive and moderate evening preferences. Dopamine has no effect on Per3 expression in healthy controls, but produces a significant difference in the ADHD group at ZT24 and ZT28. In the ADHD group, incubation with dopamine, either 1 µM or 10 µM, resulted in an adjustment of Per3 expression to control levels. A similar effect also was found in the expression of Per2. Statistical significant differences in the expression of Per2 (ZT4) in the control group compared to the ADHD group were found, following incubation with dopamine. The present study illustrates that dopamine impacts on circadian function. The results lead to the suggestion that dopamine may improve the sleep quality as well as ADHD symptoms by adjustment of the circadian gene expression, especially for Per2 and Per3.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1808.2-1809
Author(s):  
D. Karatas ◽  
Z. Öztürk ◽  
D. Cekic ◽  
Z. Yuertsever ◽  
Ü. Erkorkmaz ◽  
...  

Background:Familial Mediterranean Fever (FMF) is a hereditary autoinflammatory disease characterized by recurrent attacks of fever, peritonitis, pleuritis, arthritis, and skin eruption (1). It is shown by studies that chronic diseases like diabetes mellitus, chronic heart disease, hypertension which other than inflammatory – rheumatologic disease increase depression and anxiety (2). There are a few studies evaluating depression and anxiety in FMF patients, and these results are conflicting (3,4).Objectives:To assess the frequency of depression and anxiety in patients with Familial Mediterranean Fever (FMF)Methods:In this study, 77 FMF patients aged 18 and over who were followed up in Sakarya University Education and Research Hospital, Department of Rheumatology, and 78 healthy volunteers aged 18 and over as thecontrol group. Beck depression scale and Beck anxiety scale were used to depression and anxiety, respectively. Beck’sdepression scale was evaluated as 9 and below normal, 10-16 mild depression, 17-29 moderate depression, 30-63 severe depression. Beck anxiety scale was evaluated as 0-8 normal, 8-15 mild anxiety, 16-25 moderate anxiety, 26 and above severe anxiety.FMF disease severity was determined by Pras scoring.Results:The study group, comprised 77 diagnosed with FMF with a meanage of 37.18 and a control group comprised of 78 healthy controls (C) with a meanage of 35.32 (p=0,058). İn studygroup (P) %63.6, control group (C) %53.8 as female. %36.4 of thestudy group(C), %46.2 of the control group are male. (p=0,216). The prevalence of depression was significantly higher in FMF patients compared to the control group (in order P;C: normal %24,7; %47,4, mild depression: %40.3; %26.9, moderate depression %26; %19.2, severe depression %11.7; %6.4 p<0.015). Similarly in depression results; the prevalence of anxiety was significantly higher in FMF patients compared to the control group (in order P;C normal %23,4; %57.7, mild anxiety %26; %20.5, moderate anxiety %26; %15.4, severe anxiety %24.4; %6.4 p<0,001). Depression status was not correlated with FMF disease severity (p=0.645). A correlation was found between FMF severity and anxiety which it is which was found statistically significant (p=0.005).There was no relationship between erythrocyte sedimentation rate and C-reactive protein with depression and anxiety.Conclusion:Both anxiety and depression frequency are increased in FMF patients compared to healthy controls.References:[1]Livneh A, Langevitz P, Zemer D et al. (1997) Criteria for the diagnosis of familial Mediterranean fever. Arthritis Rheum 40 (10), 1879–85.[2]Alonso J, Ferrer M, Gandek B, Ware JE Jr, Aaronson NK, Mosconi P, Rasmussen NK, Bullinger M, Fukuhara S, Kaasa S, Leplège A, IQOLA Project Group (2004) Health-related quality of life associated with chronic conditions in eight countries: results from the International Quality of Life Assessment (IQOLA) Project. Qual Life Res 13:283–298[3]Makay B, Emiroglu N, Unsal E (2010) Depression andanxiety in children and adolescents with familial Mediterranean fever. Clin Rheumatol 29, 375–9.[4]Giese A, Ornek A, Kilic L, Kurucay M, Sendur S. N., Lainka E, Henning B. F. Anxiety and depression in adult patients with familialMediterranean fever: a study comparing patients living in Germany and Turkey. International Journal of Rheumatic Diseases 2017; 20: 2093–2100Disclosure of Interests:None declared


2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Lilla Nóra Kovács ◽  
Dániel Baksa ◽  
Dóra Dobos ◽  
Nóra Eszlári ◽  
Kinga Gecse ◽  
...  

Abstract Background The main goal of this research was to explore whether migraineurs had a higher level of perceived stress than healthy controls during the times of the coronavirus and related restrictive measures, and to examine the relationship between different subtypes of rumination and perceived stress in these groups. We measured two facets of depressive rumination, brooding and reflection, along with rumination about the current COVID-19 situation to see whether these different subtypes of rumination explained perceived stress among migraineurs and healthy controls. Methods Healthy adults (n = 64) and migraine patients (n = 73) filled out self-report questionnaires online. A multiple linear regression model was used to test whether depressive rumination (i.e. brooding and reflection) and COVID-related rumination explained perceived stress among adults with and without migraine during the times of COVID-19, after controlling for gender, age, migraine/control group status and migraine disability. Results Although we did not find any difference in the level of perceived stress among migraineurs and the control group, perceived stress was more strongly associated with brooding as well as COVID-related rumination among migraineurs than healthy controls. COVID-related rumination and brooding (but not reflection) explained the level of perceived stress after controlling for gender, age, migraine/control group status and migraine disability. Conclusions The similar degree of perceived stress among migraineurs and the control group may imply that there is great variation in the personal experience of people regarding the pandemic, that may be determined by numerous other factors. Our results demonstrate that ruminating about the pandemic and related difficulties, as well as brooding (but not reflection) appear to be associated with higher level of perceived stress during the times of the coronavirus. This association was slightly stronger among migraineurs, hinting at the increased vulnerability of this patient group in stressful situations like the COVID-19 pandemic. Our results also suggest that ruminating about the pandemic and its consequences is weakly associated with trait-level depressive rumination, thus may be more contingent on specific factors.


2021 ◽  
Vol 9 (3) ◽  
pp. 232596712198998
Author(s):  
Joseph S. Tramer ◽  
Lafi S. Khalil ◽  
Patrick Buckley ◽  
Alexander Ziedas ◽  
Patricia A. Kolowich ◽  
...  

Background:Women’s National Basketball Association (WNBA) players have a greater incidence of lower extremity injury compared with male players, yet no data exist on functional outcomes after Achilles tendon rupture (ATR).Purpose:To evaluate the effect of Achilles tendon repair on game utilization, player performance, and career longevity in WNBA athletes.Study Design:Cohort study; Level of evidence, 3.Methods:WNBA players from 1997 to 2019 with a history of ATR (n = 12) were matched 1:2 to a healthy control group. Player characteristics, game utilization, and in-game performance data were collected for each athlete, from which the player efficiency rating (PER) was calculated. Statistical analysis was performed comparing postinjury data to preinjury baseline as well as cumulative career data. Changes at each time point relative to the preinjury baseline were also compared between groups.Results:Of the 12 players with ATR, 10 (83.3%) returned to play at the WNBA level at a mean (±SD) of 12.5 ± 3.3 months. Four players participated in only 1 WNBA season after injury. There were no differences in characteristics between the 10 players who returned to play after injury and the control group. After return to play, the WNBA players demonstrated a significant decrease in game utilization compared with preinjury, playing in 6.0 ± 6.9 fewer games, starting in 12.7 ± 15.4 fewer games, and playing 10.2 ± 9.1 fewer minutes per game ( P < .05 for all). After the index date of injury, the players with Achilles repair played 2.1 ± 1.2 more years in the WNBA, while control players played 5.35 ± 3.2 years ( P < .01) Additionally, the players with Achilles repair had a significant decrease in PER in the year after injury compared with preinjury (7.1 ± 5.3 vs 11.0 ± 4.4; P = .02). The reduction in game utilization and decrease in PER in these players was maintained when compared with the matched controls ( P < .05 for both).Conclusion:The majority of WNBA players who sustained ATR were able to return to sport after their injury; however, their career longevity was shorter than that of healthy controls. There was a significant decrease in game utilization and performance in the year after return to play compared with healthy controls.


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