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BACKGROUND/AIM: Toll-like receptor 4 (TLR4) is one of the regulators of the innate immune response. Genetic variations in TLR4 have been associated with inflammatory diseases, including type 2 diabetes. However, to our knowledge, there are no reports on the role of variations in TLR4 in chronic kidney disease susceptibility. The objective of this study is to determine whether the genetic variants in TLR4 are associated with the estimated glomerular filtration rate (eGFR), a measure of renal function. METHODS: To evaluate the association between TLR4 variants and eGFR, we used data obtained from 434 Mexican American participants from the San Antonio Family Diabetes/Gallbladder Study. GFR was estimated using the Modification of Diet in Renal Disease formula. The Asp(299)Gly (rs4986790) and Thr(399)Ile (rs4986791) variants of TLR4 were genotyped using the TaqMan assay. Association analyses between genotypes and eGFR were performed using the measured genotype approach. RESULTS: Of the two genetic markers examined for association, only the Asp(299)Gly variant of TLR4 exhibited a nominally significant association with eGFR (p = 0.025) after accounting for the covariate effects of age and sex terms, diabetes, duration of diabetes, systolic blood pressure, body mass index, and antihypertensive treatment. Carriers of Gly299 had significantly decreased eGFR values. Although, the Thr(399)Ile variant failed to exhibit a statistically significant association with eGFR, the carriers of Ile399, however, showed a trend towards decrease in eGFR. CONCLUSION: We show for the first time that Asp(299)Gly variants of TLR4 are associated with decrease in renal function in Mexican Americans.
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BACKGROUND: The estimated glomerular filtration rate (eGFR) is a well-known measure of kidney function and is commonly used for the diagnosis and management of patients with chronic kidney disease. The inter-individual variation in eGFR has significant genetic component. However, the identification of underlying genetic susceptibility variants has been challenging. In an attempt to identify and characterize susceptibility genetic variant(s) we previously identified the strongest evidence for linkage of eGFR occurring on chromosome 9q21 in the Mexican American participants of San Antonio Family Heart Study (SAFHS). The objective of the present study was to examine whether the common genetic variants in Neurotrophic Tyrosine Receptor Kinase 2 (NTRK2), a positional candidate gene on 9q21, contribute to variation in eGFR. RESULTS: Twelve tagging single nucleotide polymorphisms (SNPs) across the NTRK2 gene region were selected (r2 ≥ 0.80, minor allele frequency of ≥ 0.05) from the Hapmap database. SNPs were genotyped by TaqMan assay in the 848 Mexican American subjects participated in the SAFHS. Association analysis between the genotypes and eGFR (estimated by the Modification of Diet in Renal Disease equation) were performed by measured genotype approach as implemented in the program SOLAR. Of the 12 common genetic variants examined, the rs1036915 (located in 3'UTR) and rs1187274 (located in intron-14), present in perfect linkage disequilibrium, exhibited an association (P = 0.017) with eGFR after accounting for the effects of age, sex, diabetes, diabetes duration, systolic blood pressure and blood pressure medication. The carriers of minor allele of rs1036915 (G; 38%) had increased eGFR (104 ± 25 ml/min/1.73 m(2)) in comparison to the carriers of major allele A (98 ± 25 ml/min/1.73 m(2)). CONCLUSION: Together, our results suggest for the first time that the genetic variants in NTRK2 may regulate eGFR.
Assuntos
Predisposição Genética para Doença/epidemiologia , Taxa de Filtração Glomerular , Desequilíbrio de Ligação , Polimorfismo de Nucleotídeo Único , Receptor trkB/genética , Adulto , Feminino , Marcadores Genéticos , Predisposição Genética para Doença/genética , Humanos , Masculino , Americanos Mexicanos , Pessoa de Meia-Idade , Receptor trkB/metabolismo , Texas/epidemiologiaRESUMO
The rising global epidemic of diabetic nephropathy (DN) will likely lead to increase in the prevalence of cardiovascular morbidity and mortality posing a serious burden for public health care. Despite greater understanding of the etiology of diabetes and the development of novel treatment strategies to control blood glucose levels, the prevalence and incidence rate of DN is increasing especially in minority populations including Mexican-Americans. Mexican-Americans with type 2 diabetes (T2DM) are three times more likely to develop microalbuminuria, and four times more likely to develop clinical proteinuria compared to non-Hispanic whites. Furthermore, Mexican-Americans have a sixfold increased risk of developing renal failure secondary to T2DM compared to Caucasians. Prevention and better treatment of DN should be a high priority for both health-care organizations and society at large. Pathogenesis of DN is multi-factorial. Familial clustering of DN-related traits in MAs show that DN and related traits are heritable and that genes play a susceptibility role. While, there has been some progress in identifying genes which when mutated influence an individual's risk, major gene(s) responsible for DN are yet to be identified. Knowledge of the genetic causes of DN is essential for elucidation of its mechanisms, and for adequate classification, prognosis, and treatment. Self-identification and collaboration among researchers with suitable genomic and clinical data for meta-analyses in Mexican-Americans is critical for progress in replicating/identifying DN risk genes in this population. This paper reviews the approaches and recent efforts made to identify genetic variants contributing to risk for DN and related phenotypes in the Mexican-American population.
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Nefropatias Diabéticas/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Americanos Mexicanos/genética , Característica Quantitativa Herdável , Nefropatias Diabéticas/fisiopatologia , Ligação Genética , HumanosRESUMO
The incidence of diabetic nephropathy (DN) is growing rapidly worldwide as a consequence of the rising prevalence of Type 2 diabetes mellitus (T2DM). Among U.S. ethnic groups, Mexican Americans have a disproportionately high incidence and prevalence of DN and associated end-stage renal disease (ESRD). In communities bordering Mexico, as many as 90% of Mexican American patients with ESRD also suffer from T2DM compared to only 50% of non-Hispanic Whites (NHW). Both socio-economic factors and genetic predisposition appear to have a strong influence on this association. In addition, certain pathogenetic and clinical features of T2DM and DN are different in Mexican Americans compared to NHW, raising questions as to whether the diagnostic and treatment strategies that are standard practice in the NHW patient population may not be applicable in Mexican Americans. This article reviews the epidemiology of DN in Mexican Americans, describes the pathophysiology and associated risk factors, and identifies gaps in our knowledge and understanding that needs to be addressed by future investigations.
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Diabetes Mellitus Tipo 2/epidemiologia , Nefropatias Diabéticas/epidemiologia , Falência Renal Crônica/epidemiologia , Americanos Mexicanos/estatística & dados numéricos , Obesidade/epidemiologia , Índice de Massa Corporal , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/complicações , Humanos , Incidência , Falência Renal Crônica/complicações , Obesidade/complicações , Pobreza , Prevalência , Fatores de Risco , Texas/epidemiologia , População Branca/estatística & dados numéricosRESUMO
BACKGROUND: Evidence for linkage of albuminuria to GABRB3 marker region on chromosome 15q12 was previously reported in Mexican Americans. The objective of this study is to scan a positional candidate gene, Transient Receptor Potential cation channel, subfamily M 1 (TRPM1), for genetic variants that may contribute to the variation in albumin-to-creatinine ratio (ACR). METHODS: To identify the sequence variants, the exons and 2 kb putative promoter region of TRPM1 were PCR amplified and sequenced in 32 selected individuals. Identified variants were genotyped in the entire data set (N=670; 39 large families) by TaqMan assays. Association analyses between the sequence variants and ACR, type 2 diabetes (T2DM) and related phenotypes were carried out using a measured genotype approach as implemented in the program SOLAR. RESULTS: Sequencing analysis identified 18 single nucleotide polymorphisms (SNPs) including 8 SNPs in the coding regions, 7 SNPs in the promoter region and 3 SNPs in introns. Of the 8 SNPs identified in the coding regions, 3 were non synonymous [Met(1)Thr, Ser(32)Asn, Val(1395)Ile] and one SNP caused stop codon (Glu1375/*). Of the SNPs examined, none of them exhibited statistically significant association with ACR after accounting for the effect of age, sex, diabetes, duration of diabetes, systolic blood pressure and anti-hypertensive medications. However, a SNP (rs11070811) located in the putative promoter region showed a modest association with triglycerides levels (P=0.039). CONCLUSION: The present investigation found no evidence for an association between sequence variation at the TRPM1 gene and ACR in Mexican Americans, although it appears to have modest influence on T2DM risk factors.
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Albuminúria/genética , Canais de Cátion TRPM/genética , Idoso , Éxons , Feminino , Humanos , Masculino , Americanos Mexicanos , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo de Nucleotídeo Único , Regiões Promotoras GenéticasRESUMO
OBJECTIVE: Human 8-oxoguanine glycosylase 1 (OGG1) excises oxidatively damaged promutagenic base 8-oxoguanine, a lesion previously observed in a rat model of type 2 diabetes (T2DM). The objective of the present study is to determine whether genetic variation in OGG1 is associated with type 2 diabetes (T2DM) in a Mexican American cohort. METHODS: Ten SNPs including two tagging SNPs (rs1052133, rs2072668) across the OGG1 gene region were selected from the Hapmap database and genotyped in the entire cohort (n = 670; 29% diabetes; 39 families) by TaqMan assay. Association analyses between the SNPs and T2DM were performed using the measured genotype approach as implemented in the program SOLAR. RESULTS: Of the ten SNPs genotyped, only five were polymorphic. The minor allele frequencies of these 5 SNPs ranged from 1-38%. Of the SNPs examined for association, the Ser(326)Cys (rs1052133) exhibited significant association with T2DM (p = 0.016) after accounting for age and sex effects. Another intronic variant (rs2072668), which was in strong linkage disequilibrium (r(2) = 0.96) with Ser(326)Cys also exhibited significant association with T2DM (p = 0.031). CONCLUSIONS: These results suggest for the first time that the variants in OGG1 could influence diabetes risk in these Mexican American families and support a role for alterations of OGG1 in the pathogenesis of T2DM.
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DNA Glicosilases/genética , Diabetes Mellitus Tipo 2/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Americanos Mexicanos/genética , Polimorfismo de Nucleotídeo Único/genética , Adulto , Feminino , Humanos , Desequilíbrio de Ligação/genética , Masculino , TexasRESUMO
Several novel genes that are up-regulated in the kidney in diabetes have been identified including GREM1, which encodes gremlin 1. GREM1 maps to human chromosome 15q12, a region previously found to be linked to albumin to creatinine ratio (ACR) in Mexican Americans. The objective of this study is to investigate whether genetic variants in GREM1, a positional candidate gene, contribute to variation in ACR. By sequencing 32 individuals for both exons and 2-kilobase putative promoter region of GREM1, we identified 19 genetic variants including 5 in the promoter region and 13 in the 3' untranslated region. Of 19 polymorphisms identified, 13 polymorphisms were genotyped in the entire cohort (N = 670, 39 large families) either by restriction fragment length polymorphism or by TaqMan (Applied Biosystems, Foster City, CA) assays. Association analyses between the genotypes and ACR, type 2 diabetes mellitus, and related phenotypes were carried out using a measured genotype approach as implemented in the variance component analytical tools (SOLAR). Of the variants examined for association, none exhibited statistically significant association with ACR after accounting for the effects of covariates such as age, sex, diabetes, duration of diabetes, systolic blood pressure, and antihypertensive medications. However, 2 novel variants at the 3' untranslated region showed significant association with estimated glomerular filtration rate (P = .010 and P = .049) and body mass index (P = .013 and P = .019) after accounting for trait-specific covariate influences. Furthermore, a novel variant located in the promoter exhibited a significant association with systolic (P = .038) and diastolic blood pressure (P = .005) after adjusting for the effects of age, sex, diabetes, and antihypertensive medications. In conclusion, the variants examined at GREM1 are not significant contributors to variation in ACR in Mexican Americans, although they appear to minimally influence risk factors related to ACR.
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Albuminúria/etiologia , Albuminúria/genética , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/genética , Peptídeos e Proteínas de Sinalização Intercelular/genética , Adulto , Cromossomos Humanos Par 15/genética , Creatinina/sangue , DNA/genética , Éxons/genética , Feminino , Genótipo , Hemodinâmica/fisiologia , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/fisiologia , Desequilíbrio de Ligação/genética , Masculino , Americanos Mexicanos , Pessoa de Meia-Idade , Fenótipo , Polimorfismo Genético/genética , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
BACKGROUND/AIMS: Genetic polymorphisms in the paraoxonase 2 (PON2) gene are thought to alter its activity and contribute to the development of cardiovascular and renal disease risk. The purpose of this study is to determine whether the Arg148Gly, Cys311Ser and rs12794795 polymorphisms of PON2 examined previously by others, are associated with type 2 diabetes (T2DM), and subclinical measures of cardiovascular and renal disease risk in Mexican Americans. METHODS: Study participants (n = 848; 21 families) were genotyped for the three polymorphisms by TaqMan assay. Association between the genotypic and phenotypic data was performed by measured genotype approach as implemented in the variance component analytical tools. RESULTS: The Arg148Gly variant was found to be monomorphic in our dataset. Of the phenotypes examined for association, the A/C variant located in intron-1 (rs12794795) exhibited statistically significant association only with diastolic blood pressure (p = 0.018) after accounting for the trait-specific covariate effects. The Cys311Ser variant failed to show statistically significant association with any of the phenotypes examined. CONCLUSION: In conclusion, the variants examined at the PON2 locus in Mexican Americans do not appear to be a major contributor to T2DM, cardiovascular or renal disease risk, although they exhibited a small effect on the blood pressure values.
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Arildialquilfosfatase/genética , Doenças Cardiovasculares/genética , Predisposição Genética para Doença/genética , Nefropatias/genética , Polimorfismo Genético , Pressão Sanguínea/genética , Doenças Cardiovasculares/etnologia , Diabetes Mellitus Tipo 2/genética , Saúde da Família , Predisposição Genética para Doença/etnologia , Genótipo , Humanos , Nefropatias/etnologia , Americanos Mexicanos/genética , Epidemiologia Molecular , FenótipoRESUMO
The T-786C, Glu298Asp, and 27 bp variable number of tandem repeats (27 bp-VNTR-a/b) polymorphsims of the endothelial nitric oxide synthase (eNOS) gene are thought to alter nitric oxide production and contribute to the development of vascular and renal disease risk. The objective of this study is to investigate whether these three polymorphisms examined previously by others are associated with cardiovascular and renal disease risk in Mexican Americans. Study participants (N = 848; 21 families) were genotyped for T-786C, Glu298Asp, and 27 bp-VNTR-a/b polymorphisms by PCR followed by restriction digestion. Association analyses were performed by a measured genotype approach implemented in the program SOLAR. Of the phenotypes (type 2 diabetes, hypertension, body mass index, waist circumference, total cholesterol, high density lipoprotein cholesterol, triglycerides, systolic and diastolic blood pressure, albumin to creatinine ratio (ACR), and estimated glomerular filtration rate) examined for association, the 27 bp-VNTR-a/b variant exhibited statistically significant association with ACR (P = 0.047) after accounting for the trait specific covariate effects. In addition, the promoter variant (T-786C) showed a significant association with triglycerides (P = 0.034) after accounting for covariate influences. In conclusion, the present study adds evidence to the role of eNOS candidate gene polymorphisms in modulating the risk factors related to cardiovascular-renal disease in Mexican Americans although the magnitude of the genetic effect is small.
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Albuminas/metabolismo , Pareamento de Bases/genética , Creatinina/metabolismo , Íntrons/genética , Americanos Mexicanos/genética , Repetições Minissatélites/genética , Óxido Nítrico Sintase Tipo III/genética , Família , Feminino , Frequência do Gene , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo GenéticoRESUMO
BACKGROUND: Elevated serum uric acid is associated with several cardiovascular disease (CVD) risk factors such as hypertension, inflammation, endothelial dysfunction, insulin resistance, dyslipidemia, and obesity. However, the role of uric acid as an independent risk factor for CVD is not yet clear. OBJECTIVE: The aim of the study was to localize quantitative trait loci regulating variation in serum uric acid and also establish the relationship between serum uric acid and other CVD risk factors in Mexican Americans (n = 848; men = 310, women = 538) participating in the San Antonio Family Heart Study. METHODS: Quantitative genetic analysis was conducted using variance components decomposition method, implemented in the software program SOLAR. RESULTS: Mean +/- SD of serum uric acid was 5.35 +/- 1.38 mg/dl. Univariate genetic analysis showed serum uric acid and other CVD risk markers to be significantly heritable (P < 0.005). Bivariate analysis showed significant correlation of serum uric acid with body mass index, waist circumference, waist/hip ratio, total body fat, plasma insulin, serum triglycerides, high-density lipoprotein cholesterol, C-reactive protein, and granulocyte macrophage-colony stimulating factor (P < 0.05). A genome-wide scan for detecting quantitative trait loci regulating serum uric acid variation showed a significant logarithm of odds (LOD) score of 4.72 (empirical LOD score = 4.62; P < 0.00001) on chromosome 3p26. One LOD support interval contains 25 genes, of which an interesting candidate gene is chemokine receptor 2. SUMMARY: There is a significant genetic component in the variation in serum uric acid and evidence of pleiotropy between serum uric acid and other cardiovascular risk factors.
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Doenças Cardiovasculares/genética , Variação Genética , Americanos Mexicanos/genética , Ácido Úrico/sangue , Adulto , Doenças Cardiovasculares/sangue , Cromossomos Humanos Par 3 , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Escore Lod , Masculino , Pessoa de Meia-Idade , Locos de Características Quantitativas , Fatores de RiscoRESUMO
The aim of this study is to examine whether the ACE-I/D, AGT-M235T, and AT1R-A1166C polymorphisms of the renin-angiotensin system (RAS) genes are associated with cardiovascular and renal-related risk factors in Mexican Americans. Study participants (N = 848) were genotyped by Taqman assays. Association analyses were performed by measured genotype approach. Of the phenotypes examined, the ACE-I/D, AGT-M235T, and AT1R-A1166C polymorphisms exhibited significant association with systolic blood pressure, glomerular filtration rate and body mass index, respectively. The data suggest that the polymorphisms examined in the RAS may modulate the risk factors associated with cardiovascular-renal disease.
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Doenças Cardiovasculares/genética , Variação Genética , Nefropatias/genética , Americanos Mexicanos/genética , Sistema Renina-Angiotensina/genética , Albuminúria/genética , Alelos , Angiotensinogênio/genética , Diabetes Mellitus Tipo 2/genética , Feminino , Frequência do Gene , Genótipo , Humanos , Hipertensão/genética , Mutação INDEL , Masculino , Peptidil Dipeptidase A/genética , Polimorfismo de Nucleotídeo Único , Receptor Tipo 1 de Angiotensina/genética , Fatores de Risco , TexasRESUMO
Genetic variants of the endothelial nitric oxide synthase (eNOS) gene such as T-786C, Glu298Asp and 27bp-VNTR have been examined for their association with type 2 diabetes (T2DM)-related traits in various populations but not in Mexican Americans. However, the results from such studies have been controversial. This study investigated whether these three polymorphisms are associated with T2DM and its related traits in Mexican Americans, a population at high risk for T2DM and its complications. The study participants (n=670; 39 families) were genotyped for the three polymorphisms using polymerase chain reaction followed by restriction fragment length polymorphism assay. Association analyses between these polymorphisms and T2DM and its related phenotypes were carried out using a measured genotype approach as implemented in the computer program SOLAR. Of the variants examined, only the 27bp-VNTR variant exhibited significant association with high-density lipoprotein cholesterol (HDL-C) (p=0.04) and diastolic blood pressure (DBP) levels (p=0.02) after accounting for trait-specific covariates. The carriers of the rare allele (27bp-VNTR-4a) were found to have decreased HDL-C and increased DBP levels. In conclusion, of the genetic polymorphisms examined at the eNOS locus, only 27bp-VNTR appears to be a minor contributor to the variation in T2DM-related traits in Mexican Americans.
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Diabetes Mellitus Tipo 2/etnologia , Diabetes Mellitus Tipo 2/genética , Americanos Mexicanos/genética , Óxido Nítrico Sintase Tipo III/genética , Polimorfismo de Fragmento de Restrição , Adulto , Pressão Sanguínea/genética , HDL-Colesterol/sangue , Diabetes Mellitus Tipo 2/enzimologia , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Frequência do Gene , Predisposição Genética para Doença , Humanos , Metabolismo dos Lipídeos/genética , Masculino , Pessoa de Meia-Idade , Repetições Minissatélites , Fenótipo , Reação em Cadeia da Polimerase , Estados Unidos/epidemiologiaAssuntos
Diabetes Mellitus Tipo 2/genética , Americanos Mexicanos/estatística & dados numéricos , Polimorfismo Genético , Sistema Renina-Angiotensina/genética , Angiotensinogênio/genética , Receptores de Apelina , Creatinina/metabolismo , Família , Feminino , Predisposição Genética para Doença/genética , Genótipo , Humanos , Masculino , Peptidil Dipeptidase A/genética , Receptores Acoplados a Proteínas G/genética , TexasRESUMO
OBJECTIVE: Glomerular filtration rate (GFR) is used to assess the progression of renal disease. We performed linkage analysis to localize genes that influence GFR using estimated GFR data from the San Antonio Family Diabetes/Gallbladder Study. We also examined the effect of genotype by diabetes interaction (G x DM) on the detection of linkage to address whether genetic effects on GFR differ in diabetic and nondiabetic subjects. RESEARCH DESIGN AND METHODS: GFR (N = 453) was estimated using the recently recalculated Cockcroft-Gault (GFR-CGc) and the simplified Modification of Diet in Renal Disease (GFR-4VMDRD) formulae. Both estimates of GFR exhibited significant heritabilities, but only GFR-CGc showed significant G x DM interaction. We therefore performed multipoint linkage analyses on both GFR measures using models that did not include G x DM interaction effects (Model 1) and that included G x DM interaction effects (Model 2, in the case of GFR-CGc). RESULTS: The strongest evidence for linkage (Model 1) of both GFR-CGc (logarithm of odds [LOD] 2.9) and GFR-4VMDRD (LOD 2.6) occurred between markers D9S922 and D9S1120 on chromosome 9q. However, using Model 2, the strongest evidence for linkage of GFR-CGc on chromosome 2q was found near marker D2S427 (corrected LOD score [LOD(C)] 3.3) compared with the LOD score of 2.7 based on Model 1. Potential linkages (LOD or LOD(C) >or=1.2) were found only for GFR-CGc on chromosomes 3p, 3q, 4p, 8q, 11q, and 14q. CONCLUSIONS: We found a major locus on chromosome 2q that differentially influences GFR in diabetic and nondiabetic environments in the Mexican-American population.
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Cromossomos Humanos Par 2 , Diabetes Mellitus/genética , Taxa de Filtração Glomerular/genética , Hispânico ou Latino/genética , Adulto , Idoso , Mapeamento Cromossômico , Nefropatias Diabéticas/genética , Feminino , Genótipo , Humanos , Falência Renal Crônica/genética , Masculino , Pessoa de Meia-Idade , Valores de ReferênciaRESUMO
PURPOSE: Microalbuminuria, defined as urine albumin-to-creatinine ratio of 0.03 to 0.299 mg/mg, is a major risk factor for cardiovascular disease. Several genetic epidemiological studies have established that microalbuminuria clusters in families, suggesting a genetic predisposition. METHOD: We estimated heritability of microalbuminuria and performed a genome-wide linkage analysis to identify chromosomal regions influencing urine albumin-to-creatinine ratio in 486 Mexican Americans from 26 multiplex families. RESULTS: Significant heritability was demonstrated for urine albumin-to-creatinine ratio (h = 24%, P < 0.003) after accounting for age, sex, body mass index, triglycerides, and hypertension. Genome scan revealed significant evidence of linkage of urine albumin-to-creatinine ratio to a region on chromosome 20q12 (LOD score of 3.5, P < 0.001) near marker D20S481. This region also exhibited a LOD score of 2.8 with diabetes status as a covariate and 3.0 with hypertension status as a covariate suggesting that the effect of this locus on urine albumin-to-creatinine ratio is largely independent of diabetes and hypertension. CONCLUSION: Findings indicate that there is a gene or genes located on human chromosome 20q12 that may have functional relevance to albumin excretion in Mexican Americans. Identifying and understanding the role of the genes that determine albumin excretion would lead to the development of novel therapeutic strategies targeted at high-risk individuals in whom intensive preventive measures may be most beneficial.