The impact of single nucleotide polymorphisms on patterns of non-contact musculoskeletal soft tissue injuries in a football player population according to ethnicity

Genetic determinants appear to play a role in susceptibility to chronic diarrhea, but the genetic abnormalities involved have only been identified in a few conditions. The Na+/H+ exchanger 3 (NHE3) accounts for a large fraction of physiologic intestinal Na+ absorption. It is highly regulated through effects on its intracellular COOH-terminal regulatory domain. The impact of genetic variation in the NHE3 gene, such as single nucleotide polymorphisms (SNPs), on transporter activity remains unexplored. From a total of 458 SNPs identified in the entire NHE3 gene, we identified three nonsynonymous mutations (R474Q, V567M, and R799C), which were all in the protein's intracellular COOH-terminal domain. Here we evaluated whether these SNPs affect NHE3 activity by expressing them in a mammalian cell line that is null for all plasma membrane NHEs. These variants significantly reduced basal NHE3 transporter activity through a reduction in intrinsic NHE3 function in variant R474Q, abnormal trafficking in variant V567M, or defects in both intrinsic NHE3 function and trafficking in variant R799C. In addition, variants NHE3 R474Q and R799C failed to respond to acute dexamethasone stimulation, suggesting cells with these mutant proteins might be defective in NHE3 function during postprandial stimulation and perhaps under stressful conditions. Finally, variant R474Q was shown to exhibit an aberrant interaction with calcineurin B homologous protein (CHP), an NHE3 regulatory protein required for basal NHE3 activity. Taken together, these results demonstrate decreased transport activity in three SNPs of NHE3 and provide mechanistic insight into how these SNPs impact NHE3 function.

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COL1A1 GENE POLYMORPHISM IN MATERNITY PATIENTS WITH SOFT TISSUE INJURIES

Ulyanovsk Medico-biological Journal ◽

10.34014/2227-1848-2021-4-54-58 ◽

2021 ◽

pp. 54-58

Author(s):

Kh.M. Laypanova ◽

N.A. Zharkin ◽

Yu.A. Shatilova

Keyword(s):

Soft Tissue ◽

Gene Polymorphism ◽

Gene Mutation ◽

Pelvic Floor Muscle ◽

Soft Tissue Injuries ◽

Birth Trauma ◽

Homozygous Mutation ◽

Col1a1 Gene ◽

Tissue Injuries ◽

The Impact

The aim of the paper is to determine the impact of COL1A1 gene polymorphism on soft tissue injuries in maternity patients. Materials and Methods. The study involved 62 maternity patients who were divided into 2 groups. The first group included 45 patients (72.5 %) without type 1 collagen mutation, alpha 1 Sp1-polymorphism (G2046T) G/G. The second group consisted of 16 patients (27.5 %) with mutation in COL1A1 gene, Sp1-polymorphism (G2046T) G/T. During the study, a homozygous mutation, Sp1-polymorphism (G2046T) T/T was observed in one patient. Age, parity and mean fetal weight of women were comparable. Results. In patients with the COL1A1 mutation, Sp1-polymorphism (G2046T), the incidence of soft tissue birth injuries was 2.3 times higher than in those without such a mutation. Thus, it was confirmed that COL1A1 gene mutation contributes to the soft tissue trauma of the birth canal. It can be regarded as a prognostic criterion and as a basis for preventive measures during pregnancy. Conclusion. Birth trauma risks remain a controversial issue. One of the factors may be COL1A1 gene mutation. Key words: birth trauma, pelvic floor muscle insufficiency, collagen 1 gene polymorphism (COL1A1). Цель работы – определить роль полиморфизма гена COL1A1 у женщин с родовыми травмами мягких тканей родовых путей. Материалы и методы. В исследовании приняло участие 62 родильницы, которые были разделены на 2 группы. В первую группу включены 45 (72,5 %) родильниц, у которых мутация коллагена типа 1, альфа 1 Sp1-polymorphism (G2046T) G/G не обнаружена. Во второй группе, состоящей из 16 (27,5 %) родильниц, обнаружена мутация гена COL1A1 Sp1-polymorphism (G2046T) G/T. В процессе проведения исследования у одной пациентки обнаружена гомозиготная мутация Sp1-polymorphism (G2046T) T/T. Пациентки были сопоставимы по возрасту, паритету и средней массе плода. Результаты. У пациенток с мутацией COL1A1 Sp1-polymorphism (G2046T) частота родовых травм мягких тканей оказалась в 2,3 раза выше, чем у пациенток без мутации. Таким образом, подтверждено, что мутация данного гена имеет определенное значение в реализации риска травм мягких тканей родовых путей, что может послужить прогностическим критерием и основанием для проведения профилактических мероприятий в период беременности. Выводы. Вопрос о рисках родового травматизма остается спорным. Одним их факторов может явиться мутация гена COL1A1. Ключевые слова: родовой травматизм, недостаточность мышц тазового дна, полиморфизм гена коллагена 1 (COL1A1).

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