E. I. Seliverstov

Polymorphisms of genes involved in inflammation and blood vessel development influence the risk of varicose veins

Heredity plays an important role in the etiology of varicose veins (VVs). However, the genetic basis underlying this condition remains poorly understood. Our aim was to replicate top association signals from genome‐wide association studies (GWASs) for VVs of lower extremities using 2 independent datasets—our sample of ethnic Russian individuals (709 cases and 278 controls) and a large cohort of British residents from UK Biobank (10 861 cases and 397 594 controls). Associations of polymorphisms rs11121615, rs6712038, rs507666, rs966562, rs7111987, rs6062618, and rs6905288 were validated in the UK Biobank individuals at a Bonferroni‐corrected significance level. In Russian cohort, only rs11121615 reached a nominal significance level of P < .05. Results of original GWAS and replication studies were combined by a meta‐analysis, and polymorphisms listed above as well as rs111434909 and rs4463578 passed a genome‐wide significant threshold. Notably, the majority of these polymorphisms were located within or near genes involved in vascular development and remodeling, and regulation of inflammatory response. Our results confirm the role of these polymorphisms in genetic susceptibility to VVs and indicate the revealed genomic regions as good candidates for further fine‐mapping studies and functional analysis. Moreover, our findings implicate inflammation and abnormal vascular architecture in VVs pathogenesis.

Short-term results of isolated phlebectomy with preservation of incompetent great saphenous vein (ASVAL procedure) in primary varicose veins disease

Objective To establish an effect of isolated phlebectomy in patients with incompetent great saphenous vein (Ambulatory Selective Varices Ablation under Local anesthesia (ASVAL) procedure) on the reflux and diameter of the trunk and to assess recurrence rate of varicose veins at one year. Material and methods We conducted a prospective study on patients with primary varicose veins and with C2 or C2,3 or C2,3,4 or C2,4 classes of chronic venous disease and great saphenous vein incompetence. The study included 67 patients (51 women and 16 men; 75 limbs in total). Age varied from 17 to 71 years; mean age was 46.8 years (SD 13.9). We recorded the presence or absence of reflux in the great saphenous vein with duplex ultrasound before and after surgery. The recurrence of varicose veins was evaluated at 12 months. All the patients underwent isolated phlebectomy with preservation of incompetent great saphenous vein (ASVAL procedure) under local anesthesia. Results At one year after removing of tributaries of the incompetent trunk, 66% of them were competent. Reflux persisted in 17% of great saphenous veins with reflux above mid-thigh and in 61% of trunks with reflux extended below the mid-thigh (p = 0.0004). The diameter of all the veins decreased significantly no matter reflux disappeared or not. Varicose veins reoccurred in 13.5% cases. In 6.5% of limbs with a reflux above the mid-thigh, the recurrence was registered at one year, while in the limbs with the reflux below the mid-thigh at a baseline, the recurrence rate was 25% (p = 0.036). Conclusion Isolated phlebectomy with a preservation of incompetent great saphenous vein leads to disappearance of reflux in a majority of cases and to significant decrease of vein diameter in all the cases. ASVAL procedure could be considered as a less aggressive and less expensive approach in selected cases. Clear indications for isolated phlebectomy need to be established.

Genome-wide association study in ethnic Russians suggests an association of the MHC class III genomic region with the risk of primary varicose veins

Heredity is a well-known risk factor for varicose veins, but genetic basis of this condition remains poorly studied. Our aim was to conduct a large-scale genetic association study for primary varicose veins (PVVs) in the population of ethnic Russians. An initial scan using Illumina HumanExome-12 v1.0 BeadChip was performed for 273 patients with PVVs and 250 controls without a history of chronic venous disease and other venous disorders. After quality control and removal of monomorphic markers, 25,424 common and 48,232 rare variants were included in the analysis. 42 single nucleotide polymorphisms (SNPs) were genotyped in the independent replication cohort of 447 PVVs patients and 443 controls. Association of common variants with PVVs was investigated by logistic regression, and the impact of rare variants was analyzed using sequence kernel association test. No effect of low frequency alleles has been revealed in our study. Common variant analysis identified a promising signal at chromosome 6 within classical major histocompatibility complex (MHC) class III subregion. The most strongly associated SNP in a combined analysis that reached a suggestive significance level of 3.2e-05 was polymorphism rs4151657 in the complement factor B gene. Testing for potential pleiotropy with other traits indicated that the same causal variant in this region increases the risk of rheumatoid arthritis and has a negative impact on human height. Our results provide suggestive evidence for the involvement of the MHC class III genes in the pathogenesis of PVVs. Further independent studies are needed to confirm our pilot findings.

Correction to: Polymorphisms of genes involved in inflammation and blood vessel development influence the risk of varicose veins

Laboratory of Pharmacogenomics, Institute of Chemical Biology and Fundamental Medicine, Theoretical and Applied Functional Genomics Laboratory, Novosibirsk State University, Novosibirsk, Russia Laboratory of Recombination and Segregation Analysis, Institute of Cytology and Genetics, Theoretical and Applied Functional Genomics Laboratory, Novosibirsk State University, Novosibirsk, Russia Laboratory of Pharmacogenomics, Institute of Chemical Biology and Fundamental Medicine, Department of Fundamental Medicine, Novosibirsk State University, Novosibirsk, Russia Laboratory of Pharmacogenomics, Institute of Chemical Biology and Fundamental Medicine, Department of Natural Sciences, Novosibirsk State University, Novosibirsk, Russia Department of Faculty Surgery, Pirogov Russian National Research Medical University, Moscow, Russia Private Surgery Center “Medalp”, Saint Petersburg, Russia Department of Faculty Surgery, Pirogov Russian National Research Medical University, Laboratory of Pharmacogenomics, Institute of Chemical Biology and Fundamental Medicine, Novosibirsk, Russia Correspondence: Alexandra Shadrina, Laboratory of Pharmacogenomics, Institute of Chemical Biology and Fundamental Medicine, 8 Lavrentjev Avenue, Novosibirsk 630090, Russia. Email: weiner.alexserg@gmail.com Funding information Russian Science Foundation

Polymorphism of Matrix Metalloproteinases Genes MMP1, MMP2, MMP3, and MMP7 and the Risk of Varicose Veins of Lower Extremities

We studied the effects of single nucleotide polymorphisms in the promoter regions of matrix metalloproteinase genes rs1799750 (-1607dupG) MMP1, rs243865 (C-1306T) MMP2, rs3025058 (-1171dupA) MMP3, and rs11568818 (A-181G) MMP7 on the risk of varicose vein of the lower extremities in ethnical Russians, residents of the Russian Federation. We genotyped 536 patients with this pathology and 273 healthy participants without history of chronic venous disease. Association was examined using logistic regression analysis. None of the studied polymorphisms showed statistically significant association with the risk of varicose veins of the lower extremities. Our results provide evidence that these polymorphisms are not involved in the pathogenesis of varicose veins and cannot serve as markers of predisposition to this pathology.

[Incidence of abdominal wall hernias: the results of population study].

AIM to define the incidence of abdominal wall hernias among ethnically homogeneous population older than 10 years within single locality. MATERIAL AND METHODS One-stage investigation of abdominal wall hernias incidence was performed in June-July 2015 in the Kryukovskoye rural settlement of the Borisovskiy district of the Belgorod region. Citizens were examined in FAPs or at home. Specially designed questionnaire was used for every person. Presence of hernia was confirmed by clinical signs or anamnestic data about previous abdominal wall repair. RESULTS AND DISCUSSION 783 (86.6%) persons were surveyed. There were 298 (38%) men and 485 (62%) women among them aged 10-90 years. Clinical signs or anamnestic data were revealed in 164 (20.9%) persons. Inguinal (n=80, 10.2%) and umbilical (n=65, 8.3%) hernias were predominant. Postoperative ventral hernia was diagnosed in 19 (2.4%) humans. CONCLUSION Incidence of abdominal wall hernias was 20.9% in our study.

Веносохраняющая и радикальная стратегии в хирургии варикозной болезни

Флебология, 4, 2016 Одним из базовых принципов лечения варикозной болезни нижних конечностей служит ликвидация узловатой трансформации подкожных вен. Это возможно только инвазивными методами, которые можно разделить на две большие группы: флебосклерозирующие и оперативные. За последними признается ведущая роль в силу их более высокой эффективности и меньшей вероятности рецидивов, в особенности ранних. На протяжении без малого 100 лет в арсенале хирургов всего мира были представлены только различные варианты удаления и перевязки вен — кроссэктомия, стриппинг, флебэктомия (удаление притоков), диссекция перфорантных вен. Одномоментное их выполнение известно ОбзОр литературы