Heritability of measures of kidney disease among Zuni Indians: the Zuni Kidney Project.

BACKGROUND: The long-term goal of the GKDZI (Genetics of Kidney Disease in Zuni Indians) Study is to identify genes, environmental factors, and genetic-environmental interactions that modulate susceptibility to renal disease and intermediate phenotypes. STUDY DESIGN: A community-based participatory research approach was used to recruit family members of individuals with kidney disease. SETTING & PARTICIPANTS: The study was conducted in the Zuni Indians, a small endogamous tribe located in rural New Mexico. We recruited members of extended families, ascertained through a proband with kidney disease and at least 1 sibling with kidney disease. 821 participants were recruited, comprising 7,702 relative pairs. PREDICTOR OUTCOMES & MEASUREMENTS: Urine albumin-creatinine ratio (UACR) and hematuria were determined in 3 urine samples and expressed as a true ratio. Glomerular filtration rate (GFR) was estimated using the Modification of Diet in Renal Disease (MDRD) Study equation modified for American Indians. Probands were considered to have kidney disease if UACR was >or=0.2 in 2 or more of 3 spot urine samples or estimated GFR was decreased according to the CRIC (Chronic Renal Insufficiency Cohort) Study criteria. RESULTS: Kidney disease was identified in 192 participants (23.4%). There were significant heritabilities for estimated GFR, UACR, serum creatinine, serum urea nitrogen, and uric acid and a variety of phenotypes related to obesity, diabetes, and cardiovascular disease. There were significant genetic correlations of some kidney-related phenotypes with these other phenotypes. LIMITATIONS: Limitations include absence of renal biopsy, possible misclassification bias, lack of direct GFR measurements, and failure to include all possible environmental interactions. CONCLUSIONS: Many phenotypes related to kidney disease showed significant heritabilities in Zuni Indians, and there were significant genetic correlations with phenotypes related to obesity, diabetes, and cardiovascular disease. The study design serves as a paradigm for the conduct of research in relatively isolated, endogamous, underserved populations.

Distribution of glyoxalase I polymorphism among Zuni Indians: the Zuni Kidney Project.

Zuni Indians are experiencing simultaneous epidemics of type 2 diabetes mellitus (T2DM) and renal disease [Scavini, M., Stidley, C. A., Shah, V. O., Narva, A. S., Tentori, F., Kessler, D. S., et al. (2003). Prevalence of diabetes is higher among female than male Zuni Indians: Diabetes among Zuni Indians. Diabetes Care, 26 (1), 55-60; Shah, V. O., Scavini, M., Stidley, C., Tentori, F., Welty, T., Maccluer, J. W., et al. (2003). Epidemic of diabetic and nondiabetic renal disease among the Zuni Indians: The Zuni Kidney Project. Journal of the American Society of Nephrology, 14, 1320-1329]. Methylglyoxal (MG), a highly reactive, cytotoxic, cross-linking endogenous aldehyde involved in the modification of biologic macromolecules, is elevated among patients with T2DM. Glyoxalase I (Glo1) is the initial enzyme involved in the detoxification of MG. Glo1 is a dimeric enzyme with three isoforms Glo1-1, Glo2-1, and Glo2-2, resulting from a point mutation (A-->C) at position 332 of cDNA. The present study was conducted to explore the hypothesis that specific polymorphisms of the Glo1 gene are associated with diabetes and/or albuminuria in Zuni Indians. We studied four groups of Zuni Indians stratified by diabetes status and albuminuria, as assessed by the urinary albumin:creatinine ratio (UACR): Group I--normal controls; Group II--T2DM and UACR<0.03; Group III--T2DM and UACR>or=0.03; and Group IV--nondiabetic participants with UACR>or=0.03. Genomic DNA was used as template for polymerase chain reaction amplification of the Glo1 gene. Products were digested to yield 110-bp bands (homozygous, CC); 54- and 45-bp bands (homozygous, AA); or all three bands (heterozygous CA). Data on age, gender, UACR, serum creatinine, hemoglobin A1(c), serum glucose, systolic and diastolic blood pressures, and the duration of T2DM among participants in Groups II and III were analyzed using analysis of variance. A generalized linear model logistic regression analysis was used to assess the relationships between specific Glo1 polymorphisms to T2DM and UACR. All three Glo1 genotypes were present among Zuni Indians. There were no significant differences in the distributions of Glo1 genotypes among the study groups (chi-square test, P=.5590). The prevalence of Glo1 A allele was higher among diabetic participants (Groups II and III combined) than among nondiabetic participants (Groups I and IV combined) (chi-square test, P=.0233). There was an association (odds ratio=2.9; 95% confidence interval=1.3-7.2) between the Glo1 A allele and T2DM.

Prevalence of diabetes is higher among female than male Zuni indians.

OBJECTIVE: Test the hypothesis that diabetes and related risk factors are more common among female than male Zuni Indians. RESEARCH DESIGN AND METHODS: We conducted a population-based, cross-sectional survey of the Zuni Indians aged > or =5 years. We used households within neighborhood clusters as the sampling frame. We administered a questionnaire, collected blood and urine, and measured height and weight. Self-reported diabetes was used to assess previously diagnosed diabetes. Participants without a prior history of diabetes were classified as having newly diagnosed diabetes if they had HbA(1c) >7.0% or random glucose > or =11.1 mmol/l during the survey. RESULTS: The prevalence of previously diagnosed diabetes among Zuni Indians aged > or =5 years (n = 1,503) was higher among female Zuni Indians (16.7% [95% CI 14.1-19.3]) than male Zuni Indians (9.7% [7.4-12.1]) (P < 0.001). The prevalence of newly diagnosed diabetes was similar among female Zuni Indians (2.4% [1.4-3.4]) and male Zuni Indians (2.4% [1.2-3.6]). The prevalence of previously and newly diagnosed diabetes was higher among female Zuni Indians (19.1% [16.4-21.9]) than male Zuni Indians (12.2% [9.5-14.8]) (P < 0.001). The prevalence of obesity was higher among female Zuni Indians (34.3% [30.9-37.7]) than male Zuni Indians (21.5% [18.4-24.7]) (P < 0.001). Obesity was associated with diabetes among female and male Zuni Indians. Physical inactivity was more common among female Zuni Indians (44.2% [40.7-47.8]) than male Zuni Indians (35.1% [31.5-38.7]) (P < 0.001). However, physical inactivity was not associated with diabetes among either female or male Zuni Indians. Gestational diabetes was a risk factor among female Zuni Indians. CONCLUSIONS: Among the Zuni Indians, the prevalence of diabetes was 57% higher among female than male members of the population. Culture, tradition, and lifestyle differences may contribute to the higher prevalence of diabetes and obesity among female Zuni Indians.