The functional variant of the CLC-Kb channel T481S is not associated with blood pressure or hypertension in Swedes

Fava, Cristiano; Montagnana, Martina; Almgren, Peter; Rosberg, L.; Guidi, Gian Cesare; Berglund, Göran; Melander, Olle

doi:10.1097/hjh.0b013e3280103a5a

Cited by 25 publications

(17 citation statements)

References 26 publications

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“…Several more recent studies with larger sample groups have not found a link with hypertension [10][11][12]. Our data appears to confirm this observation.…”

Section: Discussionsupporting

confidence: 82%

“…However, the small size of their study population leaves room for uncertainty [13]. Our findings agree with a recent study of larger sample size and add further evidence that this polymorphism is not a predictor of BP [12].…”

Section: Discussionsupporting

confidence: 82%

“…We also sought to clarify any link between this polymorphism and either current BP or history of hypertension in view of the varied findings of other studies [2,[10][11][12]. Our study found no association between the ClC-Kb T481S polymorphism and ischaemic stroke or, following stratification, lacunar stroke.…”

Section: Discussioncontrasting

confidence: 36%

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The ClC-KbT481S Chloride Channel Gene Polymorphism, Ischaemic Stroke and Hypertension

Milton¹,

Hamilton‐Bruce²,

Koblar³

et al. 2008

TONEURJ

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Stroke is a polygenic disorder. Previous genetic studies focused on candidate genes influencing pathogenic processes, with little emphasis on genes influencing vascular risk factors. Previous research linked the ClC-Kb T481S polymorphism to blood pressure (BP). We therefore undertook an association study to determine the relevance of this polymorphism to stroke, particularly lacunar stroke, given its strong correlation with hypertension. We genotyped DNA from 180 patients with acute ischaemic stroke (44 having lacunar stroke) and 298 age-and gender-matched controls using a sequence-specific polymerase chain reaction method (SS-PCR). We found no association between the ClC-Kb T481S polymorphism and ischaemic stroke (Odds Ratio (OR): 0.87, 95% Confidence Interval (CI): 0.57-1.33). Stratification for stroke subtype did not alter this finding. This polymorphism showed a borderline association with history of hypertension (p=0.06) but was not associated with systolic or diastolic BP (p>0.05). To our knowledge there are no other studies published on this polymorphism and stroke.

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“…Several more recent studies with larger sample groups have not found a link with hypertension [10][11][12]. Our data appears to confirm this observation.…”

Section: Discussionsupporting

confidence: 82%

Section: Discussionsupporting

confidence: 82%

See 1 more Smart Citation

The ClC-KbT481S Chloride Channel Gene Polymorphism, Ischaemic Stroke and Hypertension

Milton¹,

Hamilton‐Bruce²,

Koblar³

et al. 2008

TONEURJ

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“…This suggestion is further supported by the observation of an association between a common ClC-Kb polymorphism that increases channel activity and a predisposition to hypertension (7,37,62,73,126). However, it should be noted that such a predisposition has not been detected in all studies (17,37,73,132). It has been suggested that salt-loading conditions as well as sex and ethic segregation need to be considered, and that larger studies are necessary to resolve the issue (73,126,150).…”

Section: Clc-ka/bmentioning

confidence: 58%

“…The low blood pressure associated with defective ClC-Kb function suggests ClC-Kb is a target for antihypertensive drugs (41,81). This suggestion is further supported by the observation of an association between a common ClC-Kb polymorphism that increases channel activity and a predisposition to hypertension (7,37,62,73,126). However, it should be noted that such a predisposition has not been detected in all studies (17,37,73,132).…”

Section: Clc-ka/bmentioning

confidence: 68%

Novel diuretic targets

Denton

Pao

Maduke

2013

American Journal of Physiology-Renal Physiology

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As the molecular revolution continues to inform a deeper understanding of disease mechanisms and pathways, there exist unprecedented opportunities for translating discoveries at the bench into novel therapies for improving human health. Despite the availability of several different classes of antihypertensive medications, only about half of the 67 million Americans with hypertension manage their blood pressure appropriately. A broader selection of structurally diverse antihypertensive drugs acting through different mechanisms would provide clinicians with greater flexibility in developing effective treatment regimens for an increasingly diverse and aging patient population. An emerging body of physiological, genetic, and pharmacological evidence has implicated several renal ion-transport proteins, or regulators thereof, as novel, yet clinically unexploited, diuretic targets. These include the renal outer medullary potassium channel, ROMK (Kir1.1), Kir4.1/5.1 potassium channels, ClC-Ka/b chloride channels, UTA/B urea transporters, the chloride/bicarbonate exchanger pendrin, and the STE20/SPS1-related proline/alanine-rich kinase (SPAK). The molecular pharmacology of these putative targets is poorly developed or lacking altogether; however, recent efforts by a few academic and pharmaceutical laboratories have begun to lessen this critical barrier. Here, we review the evidence in support of the aforementioned proteins as novel diuretic targets and highlight examples where progress toward developing small-molecule pharmacology has been made.

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Chloride Transport

Edwards

2012

Comprehensive Physiology

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Chloride transport along the nephron is one of the key actions of the kidney that regulates extracellular volume and blood pressure. To maintain steady state, the kidney needs to reabsorb the vast majority of the filtered load of chloride. This is accomplished by the integrated function of sequential chloride transport activities along the nephron. The detailed mechanisms of transport in each segment generate unique patterns of interactions between chloride and numerous other individual components that are transported by the kidney. Consequently, chloride transport is inextricably intertwined with that of sodium, potassium, protons, calcium, and water. These interactions not only allow for exquisitely precise regulation but also determine the particular patterns in which the system can fail in disease states. © 2012 American Physiological Society. Compr Physiol 2:1061‐1092, 2012.

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The functional variant of the CLC-Kb channel T481S is not associated with blood pressure or hypertension in Swedes

Abstract: Our data do not support a role of the CLC-Kb T481S polymorphism in BP regulation in Swedes.

Cited by 25 publications

References 26 publications

The ClC-KbT481S Chloride Channel Gene Polymorphism, Ischaemic Stroke and Hypertension

The ClC-KbT481S Chloride Channel Gene Polymorphism, Ischaemic Stroke and Hypertension

Novel diuretic targets

Chloride Transport

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