Heritability of renal function in hypertensive families of African descent in the Seychelles (Indian Ocean)

Bochud, Murielle; Elston, Robert C.; Maillard, Marc; Bovet, Pascal; Schild, Laurent; Shamlaye, Conrad; Burnier, Michel

doi:10.1111/j.1523-1755.2005.00055.x

Cited by 55 publications

(43 citation statements)

References 32 publications

(24 reference statements)

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“…A major limitation of this and previous linkage studies to localize CKD genes relates to measurement of the disease phenotype(s). eGFR that are based on serum creatinine or creatinine clearance are only modestly correlated with measured GFR (r approximately 0.50 to 0.75), (45), and UACR is not perfectly correlated with albumin excretion rate (46). Because the phenotypes that we analyzed are influenced by factors that may have different genetic regulation (e.g., creatinine production and tubular excretion [47]), our findings may not be specific for glomerular filtration or albumin excretion rate.…”

Section: Discussionmentioning

confidence: 72%

Influence of Genomic Loci on Measures of Chronic Kidney Disease in Hypertensive Sibships

Turner¹,

Kardia²,

Mosley³

et al. 2006

Journal of the American Society of Nephrology

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Genomewide linkage analyses were conducted of serum creatinine, estimated GFR (eGFR), and urine albumin-creatinine ratio (UACR) in search of genetic susceptibility loci for chronic kidney disease in 1351 black (median age 63 yr, 70% women, 79% hypertensive) and 1022 white individuals (median age 61 yr, 56% women, 75% hypertensive) from sibships in which two or more members had essential hypertension diagnosed before age 60 yr. After adjustment for gender, age, diabetes, and use of angiotensin inhibitors, the logarithm-transformed measure of serum creatinine was heritable in both ethnic groups (0.45 in black individuals [P < 0.001]; 0.39 in white individuals [P < 0.001]), as was eGFR (0.52 in black individuals [P < 0.001]; 0.39 in white individuals [P < 0.001]). Log UACR was heritable in black individuals (0.30, P < 0.001) but not in white individuals (0.12; P ‫؍‬ 0.059). In black individuals, the univariate maximum multipoint logarithm of odds scores (MLS) were observed on chromosome 7 for log serum creatinine (MLS ‫؍‬ 3.65, at 43 cM from pter; P ‫؍‬ 0.00002) and eGFR (MLS ‫؍‬ 2.52, at 45 cM from pter; P ‫؍‬ 0.00033) and for log UACR (MLS ‫؍‬ 2.91, at 112 cM from pter; P ‫؍‬ 0.00012). In white individuals, only one MLS for log serum creatinine and one for eGFR achieved the logarithm of odds score criterion for "suggestive" evidence of linkage (2 < MLS < 3), both on chromosome 3 (at 211 and 209 cM, respectively); however, none did so for log UACR. In black individuals, bivariate linkage analyses of log serum creatinine and pulse pressure (i.e., systolic-diastolic BP) provided "suggestive" evidence of a region on chromosome 5 with pleiotropic effects on both traits (MLS ‫؍‬ 3.62, at 85 cM from pter; P ‫؍‬ 0.00023). These findings support the utility of genetic linkage analyses for identification of novel risk factors that influence measures of chronic kidney disease, particularly among black individuals.

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Section: Discussionmentioning

confidence: 72%

Influence of Genomic Loci on Measures of Chronic Kidney Disease in Hypertensive Sibships

Turner¹,

Kardia²,

Mosley³

et al. 2006

Journal of the American Society of Nephrology

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“…Heritability estimates for albuminuria were significant, ranging from 0.3 to 0.44 in Finnish (9), New England (10), and southeastern US (11) families enriched for members with type 2 diabetes, and the estimate was higher (h 2 ϭ 0.49) in Hypertension Genetic Epidemiology Network (Hyper-GEN) families enriched for multiple siblings with hypertension (12). Similarly, GFR was significantly heritable in families with diabetes and hypertension, ranging from 0.36 to 0.75 (11,13,14). These results are impressive, considering that albuminuria and GFR change during the course of DN.…”

Section: Familial Aggregation Of Dnmentioning

confidence: 97%

Genetic Factors in Diabetic Nephropathy

Freedman

Bostrom

Daeihagh

et al. 2007

Clinical Journal of the American Society of Nephrology

174

125

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Several genes that predispose to type 2 diabetes have recently been identified. In addition to the recognized and powerful effects of environmental factors, there is abundant evidence in support of genetic susceptibility to the microvascular complication of nephropathy in individuals with both type 1 and type 2 diabetes. Familial aggregation of phenotypes such as end-stage renal disease, albuminuria, and chronic kidney disease have routinely been reported in populations throughout the world, and heritability estimates for albuminuria and glomerular filtration rate demonstrate strong contributions of inherited factors. Recent genome-wide linkage scans have identified several chromosomal regions that likely contain diabetic nephropathy susceptibility genes, and association analyses have evaluated positional candidate genes under these linkage peaks. These complimentary approaches have demonstrated that polymorphisms in the carnosinase 1 gene on chromosome 18q, the adiponectin gene on 3q, and the engulfment and cell motility gene on 7p are likely associated with susceptibility to diabetic nephropathy. Additional genes that seem to be of importance in renal phenotypes include manganese superoxide dismutase and angiotensin 1-converting enzyme, with nitric oxide synthase implicated in albuminuria. This article reviews the inherited aspects of diabetic kidney disease with particular emphasis on recently implicated genes and pathways. It seems likely that the risk for diabetes-associated kidney disease is magnified by inheriting risk alleles at several susceptibility loci, in the presence of hyperglycemia.Clin J Am Soc Nephrol 2: 1306 -1316, 2007. doi: 10.2215/CJN.02560607 I t was previously thought that individuals who had diabetes and developed progressive diabetic nephropathy (DN) and/or ESRD were simply exposed to long durations of diabetes with relatively poor glycemic control. In other words, all individuals with diabetes were assumed to be at essentially equivalent risk for developing nephropathy, allowing for differences in their ambient serum glucose concentration. In support of the concept that exposure to a hyperglycemic environment led to DN (often with coexisting obesity, metabolic syndrome, hypertension, and hyperlipidemia), clinical trials have conclusively demonstrated that improving glycemic control delays and, in some cases, may prevent the subsequent development of albuminuria, DN, and macrovascular complications such as coronary artery disease (1,2). The concept that select individuals with diabetes were at differential risk for developing nephropathy on the basis of familial aggregation of kidney disease was initially reported in 1989 but has only recently gained broad acceptance among nephrologists and diabetologists (3). Familial Aggregation of DNThe notion that genetic factors contribute to any complex disease rests on the demonstration of familial aggregation. Familial clustering of nephropathy could result from shared genes, environmental exposures, or their combination.After repeated demonstra...

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“…We also used the abbreviated Modification of Diet in Renal Disease equation to estimate GFR. 24 In 257 participants (nϭ89, 84, and 84 in T1, T2, and T3, respectively), GFR was measured as described previously 23 using inulin clearance under fasting conditions in the morning after 24-hour urine collection and Results are means (SD) unless otherwise specified. D/N U Na V indicates day/night ratio of urinary sodium excretion rate; P, plasma concentration; FBG, fasting blood glucose; MDRD, simplified Modification of Diet in Renal Disease equation.…”

Section: Methodsmentioning

confidence: 99%

“…The selection process for families has been described previously. 23 The study originally aimed at examining genetic determinants of hypertension in families including Ն2 hypertensive siblings. Subjects Ͻ18 years of age or with an acute medical condition (eg, acute stroke or myocardial infarction within the past 6 months) were excluded from the study.…”

Section: Methodsmentioning

confidence: 99%

“…Additional methodological criteria have been described previously. 23 For the analyses, we used the average of 10 daytime and 10 nighttime randomly selected measures to have the same number of measures for each participant and each period. Sensitivity analyses conducted using all of the available daytime and nighttime BP measures led to very similar results and did not alter our conclusions.…”

Section: Methodsmentioning

confidence: 99%

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Nighttime Blood Pressure and Nocturnal Dipping Are Associated With Daytime Urinary Sodium Excretion in African Subjects

et al. 2008

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Abstract-Blood pressure (BP) follows a circadian rhythm, with 10% to 15% lower values during nighttime than during daytime. The absence of a nocturnal BP decrease (dipping) is associated with target organ damage, but the determinants of dipping are poorly understood. We assessed whether the nighttime BP and the dipping are associated with the circadian pattern of sodium excretion. Ambulatory BP and daytime and nighttime urinary electrolyte excretion were measured simultaneously in 325 individuals of African descent from 73 families. When divided into sex-specific tertiles of day:night ratios of urinary sodium excretion rate, subjects in tertile 1 (with the lowest ratio) were 6.5 years older and had a 9.8-mm Hg higher nighttime systolic BP (SBP) and a 23% lower SBP dipping (expressed in percentage of day value) compared with subjects in tertile 3 (P for trend Ͻ0.01). After adjustment for age, the SBP difference across tertiles decreased to 5.4 mm Hg (Pϭ0.002), and the SBP dipping difference decreased to 17% (Pϭ0.05). A similar trend across tertiles was found with diastolic BP. In multivariate analyses, daytime urinary sodium and potassium concentrations were independently associated with nighttime SBP and SBP dipping (PϽ0.05 for each). These data, based on a large number of subjects, suggest that the capacity to excrete sodium during daytime is a significant determinant of nocturnal BP and dipping. This observation may help us to understand the pathophysiology and clinical consequences of nighttime BP and to develop therapeutic strategies to normalize the dipping profile in hypertensive patients. (Hypertension. 2008;51:891-898.)

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Heritability of renal function in hypertensive families of African descent in the Seychelles (Indian Ocean)

Abstract: The significant heritability estimates of GFR in our sample of families of African descent confirm the familial aggregation of this trait and justify further analyses aimed at discovering genetic determinants of GFR.

Cited by 55 publications

References 32 publications

Influence of Genomic Loci on Measures of Chronic Kidney Disease in Hypertensive Sibships

Influence of Genomic Loci on Measures of Chronic Kidney Disease in Hypertensive Sibships

Genetic Factors in Diabetic Nephropathy

Nighttime Blood Pressure and Nocturnal Dipping Are Associated With Daytime Urinary Sodium Excretion in African Subjects

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