• Journal of Genetic Medicine
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• 제10권2호
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• pp.81-87
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• 2013

Pseudohypoaldosteronism (PHA), a rare syndrome of systemic or renal mineralocorticoid resistance, is clinically characterized by hyperkalemia, metabolic acidosis, and elevated plasma aldosterone levels with either renal salt wasting or hypertension. PHA is a heterogeneous disorder both clinically and genetically and can be divided into three subgroups; PHA type 1 (PHA1), type 2 (PHA2) and type 3 (PHA3). PHA1 and PHA2 are genetic disorders, and PHA3 is a secondary disease of transient mineralocorticoid resistance mostly associated with urinary tract infections and obstructive uropathies. PHA1 includes two different forms with different severity of the disease and phenotype: a systemic type of disease with autosomal recessive inheritance (caused by mutations of the amiloride-sensitive epithelial sodium channel, ENaC) and a renal form with autosomal dominant inheritance (caused by mutations of the mineralocorticoid receptor, MR). In the kidneys, the distal nephron takes charge of the fine regulation of water absorption and ion handling under the control of aldosterone. Two major intracellular actors necessary for the action of aldosterone are the MR and the ENaC. Impairment of the intracellular aldosterone signal transduction pathway results in resistance to the action of mineralocorticoids, which leads to PHA. Herein, ion handling the distal nephron and the clinico-genetic findings of PHA are reviewed with special emphasis on PHA type 1.

• 한국환경성돌연변이발암원학회지
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• 제22권4호
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• pp.223-228
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• 2002

Hypertension is characterized by multiple genetic and environmental factors. To establish the genetic basis of hypertension in Koreans, we investigated the genetic variations of two candidate genes (aldosterone synthase (CYP11B2), ${\gamma}$ subunit of the amiloride-sensitive epithelial sodium channel (ENaC) in the Korean patients with hypertension and normotensive controls. There were no significant differences in the genotype and allele frequencies between two groups, respectively. However, there was the significant difference between Korean and Caucasian populations in allele frequency of RFLPs in the two candidate genes. Therefore, these studies also need to be confirmed in other ethnic groups, although our results do not support a possible role of these genes on hypertension in Korean population

• International Journal of Oral Biology
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• 제47권4호
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• pp.49-54
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• 2022

Taste is a basic sensation to get attracted toward nutritious foods or avoid possible harmful substances. The basic taste qualities in humans consist of sweet, bitter, umami, salty, and sour. Basically, sweet and umami tastes make food attractive, whereas bitter and sour tastes make it avoidable. Salty taste comprises basic salty and high salt taste. The basic salty taste is known as amiloride-sensitive salty taste, which is inhibited by amiloride, but the high salt taste is not sensitive to amiloride. Moreover, high salt taste can also cause avoidance behavior in human beings. Sodium, one of the most important cations in the body fluids of vertebrates, controls the volume of total body fluids and is a risk factor for cardiovascular diseases, such as hypertension. The concentration of sodium in body fluids must be under delicate control. A distinction between the salty taste and high salt taste would be a contributing mechanism to control the volume and/or osmolarity of body fluids.

• The Korean Journal of Physiology and Pharmacology
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• 제17권1호
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• pp.57-64
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• 2013

Cells can resist and even recover from stress induced by acute hypoxia, whereas chronic hypoxia often leads to irreversible damage and eventually death. Although little is known about the response(s) to acute hypoxia in neuronal cells, alterations in ion channel activity could be preferential. This study aimed to elucidate which channel type is involved in the response to acute hypoxia in rat pheochromocytomal (PC12) cells as a neuronal cell model. Using perfusing solution saturated with 95% $N_2$ and 5% $CO_2$, induction of cell hypoxia was confirmed based on increased intracellular $Ca^{2+}$ with diminished oxygen content in the perfusate. During acute hypoxia, one channel type with a conductance of about 30 pS (2.5 pA at -80 mV) was activated within the first 2~3 min following onset of hypoxia and was long-lived for more than 300 ms with high open probability ($P_o$, up to 0.8). This channel was permeable to $Na^+$ ions, but not to $K^+$, $Ca^+$, and $Cl^-$ ions, and was sensitively blocked by amiloride (200 nM). These characteristics and behaviors were quite similar to those of epithelial sodium channel (ENaC). RT-PCR and Western blot analyses confirmed that ENaC channel was endogenously expressed in PC12 cells. Taken together, a 30-pS ENaC-like channel was activated in response to acute hypoxia in PC12 cells. This is the first evidence of an acute hypoxia-activated $Na^+$ channel that can contribute to depolarization of the cell.

• Journal of Nutrition and Health
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• 제50권3호
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• pp.217-224
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• 2017

Purpose: Although it is well known thatmortality and morbidity due to cardiovascular diseases are higher in salt-sensitive subjects than in salt-resistant subjects, their underlying mechanisms related to obesity remain unclear. Here, we focused on salt-sensitive gene variants unrelated to monogenic obesity that interacted with sodium intake in humans. Methods: This review was written based on the modified $3^rd$ step of Khans' systematic review. Instead of the literature, subject genes were based on candidate genes screened from our preliminary Genome-Wide Association Study (GWAS). Finally, literature related to five genes strongly associated with salt sensitivity were analyzed to elucidate the mechanism of obesity. Results: Salt sensitivity is a measure of how blood pressure responds to salt intake, and people are either salt-sensitive or salt-resistant. Otherwise, dietary sodium restriction may not be beneficial for everyone since salt sensitivity may be associated with inherited susceptibility. According to our previous GWAS studies, 10 candidate genes and 11 single nucleotide polymorphisms (SNPs) associated with salt sensitivity were suggested, including angiotensin converting enzyme (ACE), ${\alpha}$-adducin1 (ADD1), angiotensinogen (AGT), cytochrome P450 family 11-subfamily ${\beta}$-2 ($CYP11{\beta}$-2), epithelial sodium channel (ENaC), G-protein b3 subunit (GNB3), G protein-coupled receptor kinases type 4 (GRK4 A142V, GRK4 A486V), $11{\beta}$-hydroxysteroid dehydrogenase type-2 (HSD $11{\beta}$-2), neural precursor cell-expressed developmentally down regulated 4 like (NEDD4L),and solute carrier family 12(sodium/chloride transporters)-member 3 (SLC 12A3). We found that polymorphisms of salt-sensitive genes such as ACE, $CYP11{\beta}$-2, GRK4, SLC12A3, and GNB3 may be positively associated with human obesity. Conclusion: Despite gender, ethnic, and age differences in genetics studies, hypertensive obese children and adults who are carriers of specific salt-sensitive genes are recommended to reduce their sodium intake. We believe that our findings can contribute to the prevention of early-onset of chronic diseases in obese children by facilitating personalized diet-management of obesity from childhood to adulthood.

• Childhood Kidney Diseases
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• 제24권1호
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• pp.58-61
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• 2020

Pseudohypoaldosteronism type 1 (PHA1) is a rare salt-wasting disorder caused by resistance to mineralocorticoid action. PHA1 is of two types with different levels of disease severity and phenotype as follows: systemic type with an autosomal recessive inheritance (caused by mutations of the epithelial sodium channel) and renal type with an autosomal dominant inheritance (caused by mutations in the mineralocorticoid receptor). The clinical manifestations of PHA1 vary widely; however, PHA1 commonly involves hyponatremia, hyperkalemia, metabolic acidosis and elevated levels of renin and aldosterone. The earliest signs of both type of PAH1 also comprise insufficiency weight gain due to chronic dehydration and failure to thrive during infancy. Here, we report a case of renal PAH1 in a 28-day-old male infant harboring a novel heterozygous mutation in NR3C2 gene (c.1341_1345dupAAACC in exon 2), showing only failure to thrive without the characteristic of dehydration.

• Clinical and Experimental Pediatrics
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• 제54권2호
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• pp.90-93
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• 2011

Pseudohypoaldosteronism type 1 (PHA1) is a rare form of mineralocorticoid resistance characterized in newborns by salt wasting with dehydration, hyperkalemia and failure to thrive. This disease is heterogeneous in etiology and includes autosomal dominant PHA1 owing to mutations of the NR3C2 gene encoding the mineralocorticoid receptor, autosomal recessive PHA1 due to mutations of the epithelial sodium channel (ENaC) gene, and secondary PHA1 associated with urinary tract diseases. Amongst these diseases, autosomal dominant PHA1 shows has manifestations restricted to renal tubules including a mild salt loss during infancy and that shows a gradual improvement with advancing age. Here, we report a neonatal case of PHA1 with a NR3C2 gene mutation (a heterozygous c.2146_2147insG in exon 5), in which the patient showed failure to thrive, hyponatremia, hyperkalemia, and elevated plasma renin and aldosterone levels. This is the first case of pseudohypoaldosteronism type 1 confirmed by genetic analysis in Korea.

• Childhood Kidney Diseases
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• 제17권2호
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• pp.137-142
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• 2013

전신형 PHA 1은 ENaC의 ${\alpha}$ (SCNN1A), ${\beta}$ (SCNN1B), ${\gamma}$ (SCNN1G) 아단위를 암호화하는 유전자의 변이로 경상피나트륨 수송의 결함으로 발생하게 되며 신생아기에 생명을 위협하는 염분 소실, 고칼륨혈증, 대사성 산증이 발생하게 된다. 또한 신장 뿐 아니라 대장, 침샘, 땀샘 및 호흡기상피 등의 다양한 표적 기간에서 전신적으로 알도스테론에 대한 저항성이 나타난다. 최근 전신형 PHA 1의 임상상과 유전자형 및 이환된 환아들의 장기 추적 결과에 대한 보고가 되고 있으나 질환의 희소성으로 임상 표현형을 설명하기는 어려운 실정이다. 저자들은 사망을 초래할 수 있는 심각한 전해질 이상을 보인 환아에서 PHA를 의심하여 염분 및 양이온 교환수지를 투여하여 효과적으로 전해질 교정이 되어 추적관찰 중이며, 유전자 검사를 통해 missense mutation을 나타낸 전신형 PHA1을 경험하였기에 보고하는 바이다.