Jeanette Bobelu

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.

Identifying Barriers to Healthcare to Reduce Health Disparity in Zuni Indians Using Focus Group Conducted by Community Health Workers

The Zuni Pueblo is home to an economically disadvantaged population, which faces a public health challenge from the interrelated epidemics of obesity, diabetes and kidney disease. Efforts to decrease the impact of these epidemics have been complicated by historical, economic and cultural barriers, which may limit healthcare utilization. The NIH supported Zuni Health Initiative (ZHI) conducted a study to identify barriers to healthcare in the Zuni Pueblo.

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.

Genetics of kidney disease and related cardiometabolic phenotypes in Zuni Indians: the Zuni Kidney Project

The objective of this study is to identify genetic factors associated with chronic kidney disease (CKD) and related cardiometabolic phenotypes among participants of the Genetics of Kidney Disease in Zuni Indians study. The study was conducted as a community-based participatory research project in the Zuni Indians, a small endogamous tribe in rural New Mexico. We recruited 998 members from 28 extended multigenerational families, ascertained through probands with CKD who had at least one sibling with CKD. We used the Illumina Infinium Human1M-Duo version 3.0 BeadChips to type 1.1 million single nucleotide polymorphisms (SNPs). Prevalence estimates for CKD, hyperuricemia, diabetes, and hypertension were 24%, 30%, 17% and 34%, respectively. We found a significant (p < 1.58 × 10-7) association for a SNP in a novel gene for serum creatinine (PTPLAD2). We replicated significant associations for genes with serum uric acid (SLC2A9), triglyceride levels (APOA1, BUD13, ZNF259), and total cholesterol (PVRL2). We found novel suggestive associations (p < 1.58 × 10-6) for SNPs in genes with systolic (OLFML2B), and diastolic blood pressure (NFIA). We identified a series of genes associated with CKD and related cardiometabolic phenotypes among Zuni Indians, a population with a high prevalence of kidney disease. Illuminating genetic variations that modulate the risk for these disorders may ultimately provide a basis for novel preventive strategies and therapeutic interventions.

Assessing knowledge and attitudes of diabetes in Zuni Indians using a culture-centered approach.

Introduction The Zuni Pueblo, in collaboration with the University of New Mexico, have formed the Zuni Health Initiative (ZHI) engaged in community-based participatory research to plan and implement educational interventions to reduce health disparities. We conducted the first phase of ZHI study and identified barriers to healthcare. We concluded that the burden presented by these barriers ultimately translates into a lack of patient activation and engagement in their health care including for diabetes, effectively hindering adoption of healthy behaviors. Methods Community health representatives (CHRs) led 10 one-hour focus group sessions to elicit information on diabetes knowledge and self-management strategies at which a total of 84 people participated. Audiotapes were translated and transcribed by bilingual ZHI staff. We reduced the text to thematic categories, constructed a coding dictionary and inserted the text into NVivo 9 program. Results The focus groups revealed that despite extensive personal or family experiences with diabetes or complications, participants identified knowledge gaps in the disease progression and disease management. However, we gained insight into how many Zunis conceptualize the etiology of diabetes, risk factors associated with diabetes, sources of knowledge and self-management practices. Conclusion We concluded that many of the Zuni diabetics experience significant impacts on their life when they were diagnosed with diabetes and suffered the plight of stigmatization. We further concluded that developing Zuni culture specific diabetes care should focus on family involvement with continued education.

A Home-Based Educational Intervention Improves Patient Activation Measures and Diabetes Health Indicators among Zuni Indians.

Introduction One in three people will be diagnosed with diabetes by 2050, and the proportion will likely be higher among Native Americans. Diabetes control is currently suboptimal in underserved populations despite a plethora of new therapies. Patient empowerment is a key determinant of diabetes control, but such empowerment can be difficult to achieve due to resource limitation and cultural, language and health literacy barriers. We describe a home-based educational intervention using Community Health Representatives (CHRs), leading to improvement in Patient Activation Measures scores and clinical indicators of diabetes control. Methods Sixty participants with type 2 diabetes (T2D) completed a baseline evaluation including physical exam, Point of Care (POC) testing, and the Patient Activation Measure (PAM) survey. Participants then underwent a one hour group didactic session led by Community Health Representatives (CHRs) who subsequently carried out monthly home-based educational interventions to encourage healthy lifestyles, including diet, exercise, and alcohol and cigarette avoidance until follow up at 6 months, when clinical phenotyping and the PAM survey were repeated. Results PAM scores were increased by at least one level in 35 (58%) participants, while 24 participants who started at higher baseline score did not change. Six months after intervention, mean levels of A1C decreased by 0.7 ± 1.2%; fasting blood glucose decreased by 24.0 ± 38.0 mg/dl; BMI decreased by 1.5 ± 2.1 kg/m2; total cholesterol decreased by 12.0± 28.0 mg/dl; and triglycerides decreased by 52.0 ± 71.0 mg/dl. All of these changes were statistically significant (p<0.05). Conclusion This six month, CHR led and community-oriented educational intervention helps inform standards of practice for the management of diabetes, engages diabetic populations in their own care, and reduces health disparities for the underserved population of Zuni Indians. Trial Registration ClinicalTrials.gov NCT02339311

Exercise Intervention Improves the Metabolic Profile and Body Composition of Southwestern American Indian Adolescents

Introduction/Purpose The Southwestern American Indian population carries a high prevalence of metabolic syndrome and obesity, placing this group at higher risk than the general population for developing early type 2 diabetes and cardiovascular disease, likely impacting overall lifespan. This study aims to evaluate the impact of early lifestyle interventions which promote healthy eating and regular exercise on risk factors contributing to the development of the metabolic syndrome among the adolescent Zuni Pueblo population. Materials and Methods We describe a prospective, single site, community-based cohort study performed among sixty-five adolescent Zuni Indians aged 13.9 ± 1.7 years who were recruited between March 2011 and January 2014. The study intervention consisted of a targeted, tri-weekly exercise regimen with nutritional counselling, and the primary study outcomes included changes from baseline in metabolic profile (fasting lipids, A1c), vital signs (blood pressure, resting heart rate) and anthropometric characteristics of the study group. Results 41 participants have anthropometric data measured at baseline and after completion, biochemical data are available from 30 participants, and body composition data from 26 patients. Using the paired Student’s t-test with Bonferroni correction, significant improvements were shown in pediatric BMI percentile, fasting lipid profile, A1C, total body fat, and fat free mass after six months of exercise and nutritional intervention. Conclusions A simple, standardized fitness program among Southwest American Indian adolescents was effective at reducing fasting lipids and adiposity, as well as improving glycemic indices over the course of six months.

Perspectives on Biological Monitoring in Environmental Health Research: A Focus Group Study in a Native American Community

Background: Reliance on natural resources brings Native American communities into frequent contact with environmental media, which, if contaminated, represents an exposure route for environmental pollutants. Native American communities vary in their perspectives on research and relatively little is known about the range of perspectives regarding the use of biological samples for environmental exposure assessment. Methods: Thirty-one members of Zuni Pueblo (median age = 40.0 years, range = 26–59 years) participated a series of four focus groups. Qualitative themes emerging from the focus group discussion transcripts were identified by content analysis. Results: Emergent themes included adequate informed consent, traditional beliefs, and personal choice. Conclusions: The discussions reinforced the central role of traditional values in the decision to participate in research involving biological samples for environmental exposure assessment. Decision-making required a balance between the perceived value of the proposed project and its purpose, with cultural perspectives surrounding the biological sample requested. We examine the potential for study bias and include recommendations to aid in the collaborative identification and control of unintended risks posed by the use of biological samples in environmental health studies in native communities.

Using the Centers for Disease Control and Prevention’s Stay Independent Checklist to Engage a Community of American Indians and Raise Awareness About Risk of Falls, 2016

Background The unintentional death rate from falls is higher among American Indians from the US Southwest than from other regions in the country. The Zuni Pueblo is a geographically isolated, rural American Indian community located in western New Mexico. Education and screening for falls risk is lacking in this community and may be needed to reduce falls and falls-related illness and death. Community Context Building on a 17-year relationship with the Zuni Health Initiative, meetings were held with Zuni tribal leadership, staff from the Zuni Senior Center and Zuni Home Health Services, members of the Zuni Comprehensive Community Health Center, Indian Health Service, and Zuni community health representatives (CHRs) to discuss elder falls in the community. Existing infrastructure, including CHRs who were already trained and certified in diabetes education and prevention, provided support for the study. Methods Tribal leadership agreed that CHRs would be trained to administer the Centers for Disease Control and Prevention’s (CDC’s) Stay Independent checklist to assess falls risk. They administered the checklist during one-on-one interviews in Shiwi (Zuni native language), English, or both to a convenience sample of 50 Zuni elders. Outcomes Mean age of participants was 72 (standard deviation, 7.4) years, and 78% were women. Fifty-two percent reported at least 1 fall during the past year; 66% scored 4 or more on the CDC Stay Independent checklist, indicating elevated risk for falls. CHRs reported that the checklist was easy to administer and culturally accepted by the elder participants. Interpretation This study broadened the Zuni Health Initiative to include falls risk screening. Self-reported falls were common in this small sample, and the incidence was significantly higher than the national rate. These results highlight the need for community engagement, using culturally acceptable falls screening, to promote falls education and implement falls prevention programs.