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1.  Polymorphisms in the Nonmuscle Myosin Heavy Chain 9 Gene (MYH9) Are Associated with Albuminuria in Hypertensive African Americans: The HyperGEN Study 
American Journal of Nephrology  2009;29(6):626-632.
Background
MYH9 is a podocyte-expressed gene encoding nonmuscle myosin IIA that is associated with idiopathic and human immunodeficiency virus-associated focal segmental glomerulosclerosis (FSGS) and hypertensive end-stage renal disease in African Americans.
Methods
Four single nucleotide polymorphisms comprising the major MYH9 E1 risk haplotype were tested for association with estimated glomerular filtration rate (eGFR) and urine albumin:creatinine ratio (ACR) in 2,903 HyperGEN participants (1,458 African Americans (AA) in 895 families and 1,445 European Americans (EA) in 859 families) to determine the role of MYH9 in subclinical nephropathy. Association analyses employed general linear models in unrelated probands and generalized estimating equations in families. Adjustment was performed for age, sex, diabetes, BMI, medications, and mean arterial pressure separately in each race.
Results
Mean (SD) eGFR and ACR were 74.3 (16.0) ml/min/1.73 m2 and 20.3 (119.9) mg/g in EA, and 88.6 (20.9) ml/min/1.73 m2 and 76.8 (394.5) mg/g in AA (both p < 0.0001 across ethnicities). Urine ACR was associated with rs3752462 (p = 0.01) and rs4821481 (p = 0.05) in unrelated AA and with rs4821481 (p = 0.03), rs2032487 (p = 0.04) and the E1 3224 haplotype (p = 0.013) in AA families. Single nucleotide polymorphisms and the haplotype were not associated with ACR in EA or with eGFR in either ethnic group.
Conclusions
MYH9 variants are associated with albuminuria in hypertensive AA. The strength of the association was weaker than that in FSGS and hypertensive end-stage renal disease. MYH9 risk variants appear to be associated with primary FSGS with secondary hypertension, although nephrosclerosis may develop in response to hypertension in subjects homozygous for the MYH9 E1 risk haplotype.
doi:10.1159/000194791
PMCID: PMC2749685  PMID: 19153477
African Americans; Albuminuria; Chronic kidney disease; Essential hypertension; HyperGEN study; MYH9 gene
2.  Re-sequencing of the APOL1-APOL4 and MYH9 gene regions in African Americans does not identify additional risks for CKD progression 
American journal of nephrology  2015;42(2):99-106.
Background
APOL1 G1 and G2 nephropathy risk variants are associated with non-diabetic end-stage kidney disease (ESKD) in African Americans (AAs) in an autosomal recessive pattern. Additional risk and protective genetic variants may be present near the APOL1 loci since earlier age ESKD is observed in some AAs with one APOL1 renal-risk variant and because the adjacent gene MYH9 is associated with nephropathy in populations lacking G1 and G2 variants.
Methods
Re-sequencing was performed across a ~275 kb region encompassing the APOL1-APOL4 and MYH9 genes in 154 AA cases with non-diabetic ESKD and 38 controls without nephropathy who were heterozygous for a single APOL1 G1 or G2 risk variant.
Results
Sequencing identified 3246 non-coding single nucleotide polymorphisms (SNPs), 55 coding SNPs, and 246 insertion/deletions (InDels). No new coding variations were identified. Eleven variants, including a rare APOL3 Gln58Ter null variant (rs11089781), were genotyped in a replication panel of 1571 AA ESKD cases and 1334 controls. After adjusting for APOL1 G1 and G2 risk effects, these variations were not significantly associated with ESKD. In subjects with <2 APOL1 G1 and/or G2 alleles (849 cases; 1139 controls), the APOL3 null variant was nominally associated with ESKD (recessive model, OR 1.81; p=0.026); however, analysis in 807 AA cases and 634 controls from the Family Investigation of Nephropathy and Diabetes (FIND) did not replicate this association.
Conclusion
Additional common variants in the APOL1-APOL4-MYH9 region do not contribute significantly to ESKD risk beyond the APOL1 G1 and G2 alleles.
doi:10.1159/000439448
PMCID: PMC4589514  PMID: 26343748
African Americans; APOL1; kidney disease; FSGS; genetics; DNA sequencing
3.  Electrochemical skin conductance in diabetic kidney disease 
American journal of nephrology  2015;41(6):438-447.
Background
There is a need to identify patients with diabetic kidney disease (DKD) using non-invasive, cost-effective screening tests. Sudoscan®, a device using electrochemical skin conductance (ESC) to measure sweat gland dysfunction, is valuable for detecting peripheral neuropathy. ESC was tested for association with DKD (estimated glomerular filtration rate [eGFR] <60 ml/min/1.73m2) in 383 type 2 diabetes mellitus (T2D)-affected patients; diagnostic thresholds were determined in 540 patients.
Methods
Relationships between ESC with eGFR and urine albumin:creatinine ratio (UACR) were assessed in 202 European Americans (EA) and 181 African Americans (AA) with T2D.
Results
In 92 EA DKD cases and 110 T2D non-nephropathy controls, respectively, mean(SD) ages were 68.9(9.8) and 61.1(10.8) years, HbA1c 7.4(1.2) and 7.4(1.3)%, eGFR 29.5(12.2) and 87.7(14.1) ml/min/1.73m2, and UACR 1227(1710) and 7.6(5.9) mg/g. In 57 AA cases and 124 controls, respectively, mean (SD) ages were 64.0(12.0) and 59.5(9.7) years, HbA1c 7.4(1.3) and 7.6 (1.7)%, eGFR 29.7(13.3) and 90.2(16.2) ml/min/1.73m2, and UACR 1172(1564) and 7.8(7.1) mg/g. Mean(SD) ESC (μS) was lower in cases than controls (EA: case/control hands 49.3(18.5)/62.4(16.2); feet 62.2(18.0)/73.4(13.9), both p<5.8×10−7; AA: case/control hands 39.8(19.0)/48.5(17.1); feet 53.2(21.3)/63.5(19.4), both p≤0.01). Adjusting for age, sex, BMI and HbA1c, hands and feet ESC associated with eGFR <60 ml/min/1.73m2 (p≤7.2×10−3), UACR >30 mg/g (p≤7.0×10−3), UACR >300 mg/g (p≤8.1×10−3), and continuous traits eGFR and UACR (both p≤5.0×10−9). HbA1c values were not useful for risk stratification.
Conclusions
ESC measured using Sudoscan® is strongly associated with DKD in AA and EA. ESC is a useful screening test to identify DKD in patients with T2D.
doi:10.1159/000437342
PMCID: PMC4560993  PMID: 26228248
African Americans; albuminuria; diabetes mellitus; electrochemical skin conductance; European Americans; kidney disease
4.  Kidney disease and cognitive function: African American-Diabetes Heart Study MIND 
American journal of nephrology  2014;40(3):200-207.
Aims
Albuminuria and reduced estimated glomerular filtration rate (eGFR) associate with poorer cognitive performance in European-ancestry populations with advanced nephropathy; relationships in African Americans (AAs) with type 2 diabetes (T2D) are less clear. Tests of cognitive performance, urine albumin:creatinine ratio (UACR), and CKD-EPI eGFR were measured in unrelated AAs with T2D to determine relationships.
Methods
Cross-sectional analysis of 263 unrelated AAs with T2D recruited in the African American-Diabetes Heart Study (AA-DHS) MIND. Global cognitive function (mini-mental state exam [3MSE] and Montreal Cognitive Assessment [MoCA]), memory (Rey Auditory Verbal Learning Test [RAVLT]), executive function (Stroop, verbal fluency for animals, and Digit Symbol Copy [DSC]), UACR, and eGFR were determined. Relationships between cognitive tests and renal parameters were assessed using multivariate models, adjusted for age, gender, body mass index, hemoglobin A1c, level of education, hypertension, and LDL cholesterol.
Results
Participants had a mean±SD age of 60.2±9.7 years, 62.7% were female, T2D duration was 14.3±8.9 years, eGFR 86.0±23.2 ml/min/1.73m2, and UACR 155.8±542.1 (median 8.1) mg/g. In adjusted models, higher UACR was associated with worse 3MSE (p=0.014), MoCA (p=0.0089), DSC (p=0.0004), Stroop performance time (p=0.003), Stroop errors (p=0.032), and Stroop interference (p=0.026). Higher eGFR was associated with better performance on DSC (p=0.0071).
Conclusions
In AAs with T2D, albuminuria and eGFR were associated with cognitive function, even in mild kidney disease. These data stress the need for interventions to prevent cognitive decline well before the late stages of kidney disease.
doi:10.1159/000367669
PMCID: PMC4216628  PMID: 25323981
albuminuria; glomerular filtration rate; cognition; type 2 diabetes; African Americans; kidney disease
5.  Polymorphisms in the Nonmuscle Myosin Heavy Chain 9 Gene (MYH9) Are Associated with Albuminuria in Hypertensive African Americans: The HyperGEN Study 
American journal of nephrology  2009;29(6):626-632.
Background
MYH9 is a podocyte-expressed gene encoding nonmuscle myosin IIA that is associated with idiopathic and human immunodeficiency virus-associated focal segmental glomerulosclerosis (FSGS) and hypertensive end-stage renal disease in African Americans.
Methods
Four single nucleotide polymorphisms comprising the major MYH9 E1 risk haplotype were tested for association with estimated glomerular filtration rate (eGFR) and urine albumin:creatinine ratio (ACR) in 2,903 HyperGEN participants (1,458 African Americans (AA) in 895 families and 1,445 European Americans (EA) in 859 families) to determine the role of MYH9 in subclinical nephropathy. Association analyses employed general linear models in unrelated probands and generalized estimating equations in families. Adjustment was performed for age, sex, diabetes, BMI, medications, and mean arterial pressure separately in each race.
Results
Mean (SD) eGFR and ACR were 74.3 (16.0) ml/min/1.73 m2 and 20.3 (119.9) mg/g in EA, and 88.6 (20.9) ml/min/1.73 m2 and 76.8 (394.5) mg/g in AA (both p < 0.0001 across ethnicities). Urine ACR was associated with rs3752462 (p = 0.01) and rs4821481 (p = 0.05) in unrelated AA and with rs4821481 (p = 0.03), rs2032487 (p = 0.04) and the E1 3224 haplotype (p = 0.013) in AA families. Single nucleotide polymorphisms and the haplotype were not associated with ACR in EA or with eGFR in either ethnic group.
Conclusions
MYH9 variants are associated with albuminuria in hypertensive AA. The strength of the association was weaker than that in FSGS and hypertensive end-stage renal disease. MYH9 risk variants appear to be associated with primary FSGS with secondary hypertension, although nephrosclerosis may develop in response to hypertension in subjects homozygous for the MYH9 E1 risk haplotype.
doi:10.1159/000194791
PMCID: PMC2749685  PMID: 19153477
African Americans; Albuminuria; Chronic kidney disease; Essential hypertension; HyperGEN study; MYH9 gene

Results 1-5 (5)