T594M and G442V polymorphisms of the sodium channel β subunit and hypertension in a black population

Dong, YB; Zhu, HD; Baker, Emma H.; Sagnella, Giuseppe A.; MacGregor, G. A.; Carter, ND; Wicks, PD; Cook, Derek G; Cappuccio, Francesco P.

doi:10.1038/sj.jhh.1001182

Cited by 37 publications

(30 citation statements)

References 20 publications

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“…Several genetic mutations and a variety of gene polymorphisms have been related to alterations in the renal handling of sodium. Substantial interethnic differences have been shown in several cases [40,41,42]. Some of these genetic variants could also be involved in the salt-sensitivity of black African subjects with low-renin volume expanded hypertension [43].…”

Section: Discussionmentioning

confidence: 99%

Metabolic syndrome and renal sodium handling in three ethnic groups living in England

et al. 2004

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Aim/hypothesis. Increased proximal renal sodium reabsorption is associated with central adiposity and insulin resistance in white men. Our study examined whether this association also exists in other ethnic groups with different prevalences of insulin resistance and associated metabolic abnormalities. Methods. We studied the association between fractional renal excretion of endogenous lithium (FELi) and metabolic syndrome in a population study of 1190 randomly selected men and women who where 40 to 59 years of age (426 white, 397 of African and 367 of South Asian origin). Anthropometric values, blood pressure, biochemical values, questionnaire data and timed urine collections were obtained with standardised techniques. Endogenous lithium in serum and urine was measured by absorption spectrophotometry. Metabolic markers were the homeostasis model assessment (HOMA) index, waist circumference, serum triglycerides, serum HDL cholesterol and metabolic syndrome as defined by Adult Treatment Panel III criteria.Results. In white men and women a higher rate of proximal sodium re-absorption was inversely associated with higher waist circumference, serum triglycerides and HOMA index, and with lower serum HDL cholesterol (all p≤0.001)

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Section: Discussionmentioning

confidence: 99%

Metabolic syndrome and renal sodium handling in three ethnic groups living in England

et al. 2004

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“…In other studies, this mutation was not observed in Japanese individuals (13,14). So far, therefore, the T594M mutation has been identified only in individuals of African descent (11)(12)(13)(14)(15). However, our intensive sequence study clearly showed that this mutation is also present in the Japanese population, even though SCNN1B, β-subunit of epithelial sodium channel gene; BMI, body mass index; EHT, essential hypertension; NIDDM, non-insulin dependent diabetes mellitus; HL, hyperlipidemia; OMI, old myocardial infarction; EA, effort angina; OCI, old cerebral infarction; RVHT, renovascular hypertension; IGT, impaired glucose tolerance; ASO, atherosclerotic obliterance; HT, hypertension; Hx, history; SBP, systolic blood pressure; DBP, diastolic blood pressure; CCB, calcium channel blocker; BB, β-adrenergic blocker; ARB, angiotensin II receptor blockade; AB, α1-adrenergic blocker; PRA, plasma renin activity; PAC, plasma aldosterone concentration; FBS, fasting blood sugar.…”

Section: Discussionmentioning

confidence: 99%

“…Several groups have identified other molecular variants of the β subunit of ENaC (SCNN1B) (11)(12)(13)(14)(15)(16). These variants are missense mutations, and none of them affects the PY motif.…”

Section: Introductionmentioning

confidence: 99%

Six Missense Mutations of the Epithelial Sodium Channel .BETA. and .GAMMA. Subunits in Japanese Hypertensives

et al. 2004

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Liddle's syndrome is an autosomal dominant disease characterized by sodium-sensitive early hypertension and mutations in either the -or -subunit of the amiloride-sensitive epithelial sodium channel encoded by SCNN1B and SCNN1G. We sequenced the 381 bp-coding regions in exon 13 of SCNN1B and the 381 bp-coding regions in exon 12 of SCNN1G in 948 and 953 Japanese patients with hypertension, respectively. In the SCNN1B gene, we identified three missense mutations, P592S (n 3), T594M (n 2), and E632K (n 1) in a heterozygous state in addition to four synonymous ones, Ile515 (n 1), Ser520 (n 19), Ser533 (n 1), and Thr594 (n 11). In the SCNN1G gene, we identified three missense mutations, A578V (n 1), P603S (n 1), and L609F (n 1) in a heterozygous state in addition to two synonymous ones, Ile550 (n 1) and Leu649 (n 91, heterozygous; n 2, homozygous). We did not identify the same mutations previously reported in

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“…5 Mutations of the sodium channel separate from those causing Liddle's syndrome have also been identified in black people. 6 We have previously shown that one polymorphism, the T594M polymorphism, is found in Ϸ5% of the black population 7 and is significantly associated with high blood pressure. 8 The T594M polymorphism affects the regulatory C-terminal region of the sodium channel ␤-subunit and alters a putative binding site for protein kinase C. 9 This binding site is thought to mediate inhibition of sodium channel activity.…”

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confidence: 99%

Amiloride, a Specific Drug for Hypertension in Black People With T594M Variant?

et al. 2002

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Abstract-The T594M polymorphism of the epithelial sodium channel is found in Ϸ5% of people of African origin and is significantly associated with high blood pressure. Although the T594M polymorphism could increase renal sodium absorption through affected channels, it is not known whether this polymorphism causes hypertension. Amiloride specifically inhibits overactive sodium channels and effectively controls blood pressure in Liddle's syndrome, in which hypertension is caused by separate epithelial sodium channel mutations. The aim of this study was to determine whether amiloride was effective in lowering blood pressure in individuals with the T594M polymorphism. In an open, controlled study, 14 black hypertensive individuals with the T594M polymorphism were withdrawn from their usual medication and treated with amiloride. On entry to the study, individuals taking a mean of 2 drugs had blood pressure of 142/89Ϯ3/3 mm Hg. Amiloride alone (10 mg BID) controlled blood pressure effectively to the same level (140/91Ϯ4/2 mm Hg). When amiloride was withdrawn for 2 weeks, there was a large increase in blood pressure of 17/8Ϯ4/2 mm Hg (systolic, PϽ0.05; diastolic, PϽ0.01). On restarting amiloride, blood pressure was again controlled to 140/88Ϯ6/2 mm Hg. These results demonstrate that 10 mg BID amiloride is effective in controlling blood pressure in hypertensive individuals of African origin who have the T594M polymorphism. Our study supports the concept that the T594M polymorphism contributes to the elevation of blood pressure and suggests that consideration should be given to the use of amiloride in affected individuals. (Hypertension. 2002;40:13-17.)

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T594M and G442V polymorphisms of the sodium channel β subunit and hypertension in a black population

Cited by 37 publications

References 20 publications

Metabolic syndrome and renal sodium handling in three ethnic groups living in England

Metabolic syndrome and renal sodium handling in three ethnic groups living in England

Six Missense Mutations of the Epithelial Sodium Channel .BETA. and .GAMMA. Subunits in Japanese Hypertensives

Amiloride, a Specific Drug for Hypertension in Black People With T594M Variant?

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