RESUMO
We conducted a phenome-wide Mendelian randomization analysis (MR-PheWAS) to survey health effects associated with high normal serum calcium. We found causal evidence for conditions related to renal function, bone and joint health, and cardiovascular risk. These conditions collectively suggest that tissue calcification may be a key mechanism through which serum calcium influences health. INTRODUCTION: Calcium is essential for the normal functioning of the cardiovascular system, muscles, and nerves. In this MR-PheWAS study, we sought to capture the totality of health effects associated with high normal serum calcium. METHODS: We used data from up to 337,535 UK Biobank participants, and tested for associations between calcium genetic score (calcium-GS) and 925 disease outcomes, with follow-up analyses using complementary MR methods. RESULTS: Calcium-GS was robustly associated with serum calcium concentration (F statistics = 349). After multiple testing correction (P < 1.62E-4), we saw genetic evidence for an association between high serum calcium and urinary calculus (OR per 1 mg/dl 3.5, 95%CI 1.3-9.2), renal colic (9.1, 95%CI 2.5-33.5), and allergy/adverse effect of penicillin (2.2, 95%CI 1.5-3.3). Secondary analyses with independent replication from consortia meta-analyses suggested further effects on myocardial infarction and osteoarthrosis. CONCLUSION: We found causal evidence for effects of high normal serum calcium with conditions related to renal function, bone and joint health, and cardiovascular risk, which may collectively reflect influences on tissue calcification and immune function.
Assuntos
Cálcio/sangue , Estudos de Associação Genética , Análise da Randomização Mendeliana , Adulto , Idoso , Bancos de Espécimes Biológicos , Hipersensibilidade a Drogas/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Pessoa de Meia-Idade , Infarto do Miocárdio/genética , Osteoartrite/genética , Fenômica , Cólica Renal/genética , Reino Unido , Cálculos Urinários/genéticaRESUMO
Kelley-Seegmiller syndrome (KSS) is a disorder that occurs when there is a partial deficiency of the enzyme hypoxanthine guanine phosphoribosyl transferase. It is involved in the metabolism of purines, clinically manifesting as hyperuricemia, hyperuricosuria, gout arthritis, and urolithiasis. The aim of this article is to present the case of a 33-year-old male with KSS, with left ureteral colic, and a 5-mm, 323-HU ureteral calculi, successfully managed with conservative management. It is critical to recognize that most urologists are not familiar with this inborn metabolic error and 75% of these patients will be affected by urolithiasis, thus making it a very critical and significant disease in our practice.
Assuntos
Tratamento Conservador , Gota/terapia , Hipoxantina Fosforribosiltransferase/deficiência , Rim/metabolismo , Cólica Renal/terapia , Cálculos Ureterais/terapia , Ácido Úrico/metabolismo , Urologistas , Adulto , Gota/diagnóstico , Gota/genética , Gota/metabolismo , Humanos , Hipoxantina Fosforribosiltransferase/genética , Hipoxantina Fosforribosiltransferase/metabolismo , Rim/diagnóstico por imagem , Masculino , Papel Profissional , Cólica Renal/diagnóstico , Cólica Renal/genética , Cólica Renal/metabolismo , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Cálculos Ureterais/diagnóstico , Cálculos Ureterais/genética , Cálculos Ureterais/metabolismoRESUMO
BACKGROUND AND AIMS: Endothelial nitric oxide synthase gene polymorphisms play a role in some pathophysiological processes. In this study, the possible effects of endothelial nitric oxide synthase gene polymorphisms on ureteral stone disease in patients who were admitted to the emergency department with severe pain due to renal colic are examined. MATERIALS AND METHODS: The study groups were designed as controls and patients. The control group was formed from the healthy volunteers who applied to the blood center next to the emergency service. The patient group comprised patients who were diagnosed with ureteral stone disease with severe pain. All of the genetic studies were based on extracted peripheral blood samples using the necessary procedures from the Genome and Stem Cell Center at Erciyes University (GENKOK). The data were analyzed with SPSS (IBM, ver 20, United Sate). RESULTS: The study group comprised 62 females and 138 males, and the control group comprised 64 females and 136 males. All of the stones that caused renal colic were found to be localized in the ureters and the ureterovesical junction. The genotypes of the intron 4 polymorphism were found to be as follows: 4a/4a in 10 people, 4b/4a in 115, and 4b/4b in 275 people. The GG genotype of the eNOS-G894T polymorphism was found in 108 patients in the study group and in117 of the healthy individuals. There was no statistically significant difference between the two groups regarding these data. CONCLUSION: Although this study is the first in the literature to examine the relationship between renal colic and endothelial nitric oxide synthase gene polymorphisms, our study demonstrated that no relation was found.