Improving learning about familial risks using a multicomponent approach: the GRACE program.

AIM: To enhance learning (knowledge, attitudes and practices) about the importance of family health history (FHH) information and familial risks. METHODS: A pre-post design with one group was employed in this study. Five learning sessions were conducted with a community-based sample (n = 75) recruited from five counties in Texas, USA. Each learning session included: a short online video; enactive instructions on how to use the online Surgeon General FHH tool; and a presentation on how to assess familial risks. Participants completed the pre-post knowledge, attitudes and practices questionnaires and the study's satisfaction survey, and participated in a short focus group interview. RESULTS: Participants' average age was 48.1 ± 13.3 years. Over half of the participants (79%) were female, and 55% described themselves as non-Hispanic White. Our findings showed significant changes (p < 0.05) in participants' specific knowledge about factors that affect their familial risks. Similarly, significant changes (p < 0.05) in participants' attitudes toward familial risks assessment for common disease complications and confidence in controlling these risks have been documented. Participants' reported a high level of satisfaction in using online FHH tools, yet no significant change (p > 0.05) was detected in their reported practices regarding sharing FHH information with their providers or relatives. Focus group interviews revealed that participants were uncertain about providers' or relatives' reactions to sharing FHH information. CONCLUSION: Using different learning styles may have a significant impact on improving knowledge and attitudes about familial risks.

The Gly(972)Arg variant of human IRS1 gene is associated with variation in glomerular filtration rate likely through impaired insulin receptor signaling.

The objective of this study is to identify and characterize the genetic variants related to the glomerular filtration rate (GFR) linkage on 2q37. Of the positional candidate genes, we selected IRS1 and resequenced its 2-kb promoter region and exons for sequence variants in 32 subjects. A total of 11 single nucleotide polymorphisms (SNPs) were identified. To comprehensively cover the 59-kb-long intron-1, eight additional tagging SNPs were selected from the HapMap. All the 19 SNPs were genotyped by TaqMan Assay in the entire data set (N = 670; 39 families). Association analyses between the SNPs and GFR and type 2 diabetes-related traits were performed using the measured genotype approach. Of the SNPs examined for association, only the Gly(972)Arg variant of IRS1 exhibited a significant association with GFR (P = 0.0006) and serum triglycerides levels (P = 0.003), after accounting for trait-specific covariate effects. Carriers of Arg972 had significantly decreased GFR values. Gly(972)Arg contributed to 26% of the linkage signal on 2q. Expression of IRS1 mutant Arg972 in human mesangial cells significantly reduced the insulin-stimulated phosphorylation of IRS1 and Akt kinase. Taken together, the data provide the first evidence that genetic variation in IRS1 may influence variation in GFR probably through impaired insulin receptor signaling.

Implementing quality improvement in small, autonomous primary care practices: implications for the patient-centred medical home.

BACKGROUND: Implementing improvement programmes to enhance quality of care in primary care clinics is complex. Understanding how improvement strategies can be implemented in primary care is timely given the recent national movement towards transforming primary care into patient centred medical homes (PCMH). This study examined practice members' perceptions of the opportunities and challenges associated with implementing changes in their practice. METHODS: Semi-structured interviews were conducted with a sample of 56 individuals working in 16 small, community based primary care practices. The interviews consisted of open-ended questions focused on participants' perceptions of: (1) practice vision, (2) perceived need for practice improvement and (3) barriers that hinder practice improvement. The interviews were conducted at the participating clinics and were tape-recorded, transcribed, and content analysed. RESULTS: Content analysis identified two main domains for practice improvement related to: (1) the process of care, and (2) patients' involvement in their disease management. Examples of desired process of care changes included improvement in patient tracking and follow-up, standardisation of processes of care and overall clinic documentation. Changes related to patients' involvement in their care included improving (a) health education, and (b) self-care management. Among the internal barriers were: staff readiness for change, poor communication and relationship difficulties among team members. External barriers were insurance regulations, finances and patient health literacy. CONCLUSIONS: Transforming practices to more patient-centred models of care will be a priority for primary care providers. Identifying opportunities and challenges associated with implementing change is critical for successful improvement programmes. Successful strategies for enhancing the adoption and uptake of PCMH elements should leverage areas of concordance between practice members' perceived needs and planned improvement efforts.

Veterans' experience in using the online Surgeon General's family health history tool.

AIM: To assess veterans' experience and satisfaction in using the Surgeon General's (SG) online family health history (FHH) tool, and determine the perceived facilitators and barriers to using the online SG-FHH tool. MATERIALS #ENTITYSTARTX00026; METHODS: A mixed-method using both qualitative and quantitative approaches was employed in this study. A total of 35 veterans at the VA Medical Center in San Antonio, Texas, USA were invited to enter their FHH information using the online SG-FHH tool, complete the study's satisfaction survey and participate in a short semi-structured interview. The goal of the semi-structured interviews was to assess participants perceived facilitators and barriers to using the online SG-FHH tool. All participants were also provided with a printed copy of their pedigree, which was generated by the SG-FHH tool and were encouraged to share it with their relatives and providers. RESULTS: The majority of participants (91%) said that they had access to a computer with internet capability and 77% reported that they knew how to use a computer. More than two-thirds of the participants felt that items on the SG-FHH tool were easy to read and felt that FHH categories were relevant to their family's health. Approximately 94% of participants viewed the SG-FHH tool as useful, and the majority of participants (97%) indicated that they were likely to recommend the tool to others. Content analysis of the semi-structured interviews highlighted several barriers to veterans' use of the SG-FHH tool and their FHH information. These included: lack of patients' knowledge regarding their relatives' FHH, and privacy and confidentiality concerns. CONCLUSION: This study provides information on the performance and functionality of an inexpensive and widely accessible method for FHH collection. Furthermore, our findings highlight several opportunities and challenges facing the utilization of FHH information as a clinical and genomic tool at the Veterans Health Administration (VHA). The results suggest that strategies that improve veterans' knowledge regarding the importance of their FHH information and that address their concerns about privacy and confidentiality may enhance the successful implementation of FHH information into VHA clinical practice. IMPLICATIONS: identifying a locally accepted method for FHH collection and documentation which can be conducted outside of the patient visit will reduce time burdens for providers and patients and allow for a focus on other important topics during clinic visits. Improvement in familial risk screening and assessment will enable the VHA to be prepared for personalized medicine and focus their resources on promoting critically important health behaviors for populations with the highest risk of developing chronic diseases and their complications.

Genomewide linkage scan for diabetic renal failure and albuminuria: the FIND study.

BACKGROUND: Diabetic nephropathy (DN) is a leading cause of mortality and morbidity in patients with type 1 and type 2 diabetes. The multicenter FIND consortium aims to identify genes for DN and its associated quantitative traits, e.g. the urine albumin:creatinine ratio (ACR). Herein, the results of whole-genome linkage analysis and a sparse association scan for ACR and a dichotomous DN phenotype are reported in diabetic individuals. METHODS: A genomewide scan comprising more than 5,500 autosomal single nucleotide polymorphism markers (average spacing of 0.6 cM) was performed on 1,235 nuclear and extended pedigrees (3,972 diabetic participants) ascertained for DN from African-American (AA), American-Indian (AI), European-American (EA) and Mexican-American (MA) populations. RESULTS: Strong evidence for linkage to DN was detected on chromosome 6p (p = 8.0 × 10(-5), LOD = 3.09) in EA families as well as suggestive evidence for linkage to chromosome 7p in AI families. Regions on chromosomes 3p in AA, 7q in EA, 16q in AA and 22q in MA displayed suggestive evidence of linkage for urine ACR. The linkage peak on chromosome 22q overlaps the MYH9/APOL1 gene region, previously implicated in AA diabetic and nondiabetic nephropathies. CONCLUSION: These results strengthen the evidence for previously identified genomic regions and implicate several novel loci potentially involved in the pathogenesis of DN.

Genetic variants in transient receptor potential cation channel, subfamily M 1 (TRPM1) and their risk of albuminuria-related traits in Mexican Americans.

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.

The Genome-based Knowledge Management in Cycles model: a complex adaptive systems framework for implementation of genomic applications.

The main mission of the Genomic Applications in Practice and Prevention Network™ is to advance collaborative efforts involving partners from across the public health sector to realize the promise of genomics in healthcare and disease prevention. We introduce a new framework that supports the Genomic Applications in Practice and Prevention Network mission and leverages the characteristics of the complex adaptive systems approach. We call this framework the Genome-based Knowledge Management in Cycles model (G-KNOMIC). G-KNOMIC proposes that the collaborative work of multidisciplinary teams utilizing genome-based applications will enhance translating evidence-based genomic findings by creating ongoing knowledge management cycles. Each cycle consists of knowledge synthesis, knowledge evaluation, knowledge implementation and knowledge utilization. Our framework acknowledges that all the elements in the knowledge translation process are interconnected and continuously changing. It also recognizes the importance of feedback loops, and the ability of teams to self-organize within a dynamic system. We demonstrate how this framework can be used to improve the adoption of genomic technologies into practice using two case studies of genomic uptake.

Trauma disclosure to health care professionals by veterans: clinical implications.

Trauma disclosure is the initial step toward healing trauma-related distress. This study used qualitative methods to better understand factors facilitating and inhibiting change in the disclosure process. Fifty-six veterans were interviewed about their disclosure experiences between August 2004 and 2005. Emerging themes and barriers to disclosure from 23 of these interviews are reported in this article. Barriers to trauma disclosure included lack of trust in the provider, fears about the potential negative consequences of disclosure, and trauma avoidance. Providers perceived as caring and communicating at the same level as the participants facilitated disclosure, whereas providers perceived as uncaring or disinterested inhibited disclosure. Veterans reported both positive and negative reactions to initial disclosure, but nearly all agreed that disclosure was worthwhile over the long-term. Improving patient-provider communications and creating settings that facilitate trauma disclosure may improve healing after trauma.

Do diabetic veterans use the Internet? Self-reported usage, skills, and interest in using My HealtheVet Web portal.

OBJECTIVE: The Veterans Health Administration has developed My HealtheVet (MHV), a Web-based portal that links veterans to their care in the veteran affairs (VA) system. The objective of this study was to measure diabetic veterans' access to and use of the Internet, and their interest in using MHV to help manage their diabetes. MATERIALS AND METHODS: Cross-sectional mailed survey of 201 patients with type 2 diabetes and hemoglobin A(1c) > 8.0% receiving primary care at any of five primary care clinic sites affiliated with a VA tertiary care facility. Main measures included Internet usage, access, and attitudes; computer skills; interest in using the Internet; awareness of and attitudes toward MHV; demographics; and socioeconomic status. RESULTS: A majority of respondents reported having access to the Internet at home. Nearly half of all respondents had searched online for information about diabetes, including some who did not have home Internet access. More than a third obtained "some" or "a lot" of their health-related information online. Forty-one percent reported being "very interested" in using MHV to help track their home blood glucose readings, a third of whom did not have home Internet access. Factors associated with being "very interested" were as follows: having access to the Internet at home (p < 0.001), "a lot/some" trust in the Internet as a source of health information (p = 0.002), lower age (p = 0.03), and some college (p = 0.04). Neither race (p = 0.44) nor income (p = 0.25) was significantly associated with interest in MHV. CONCLUSIONS: This study found that a diverse sample of older VA patients with sub-optimally controlled diabetes had a level of familiarity with and access to the Internet comparable to an age-matched national sample. In addition, there was a high degree of interest in using the Internet to help manage their diabetes.

Providers' behavioral beliefs regarding the delivery of genomic medicine at the Veterans Health Administration.

AIMS: To examine providers' behavioral intention toward the utilization of genomic services at the Veterans Health Administration (VHA; Washington, DC, USA) through the lens of the 'Theory of Planned Behavior'. The theory of planned behavior posits that individuals' behaviors (using genomic services) are driven by their behavioral intentions. Behavioral intentions is a function of: first, behavioral beliefs; second, normative beliefs, and third; control beliefs. MATERIALS & METHODS: Semi-structured interviews were conducted with 20 providers working in different units at the South Texas Veterans Health Care System (STVHCS; TX USA). The interviews focused on assessing providers' behavioral beliefs, normative beliefs and control beliefs regarding the delivery of genomic medicine at the STVHCS. Interview materials were tape recorded, transcribed and the content was analyzed using qualitative methods. RESULTS: All participating providers perceived genomic medicine to be an important area in medicine (behavioral beliefs). They agreed that the VHA has the necessary infrastructure to foster the delivery of genomic services. The majority of participants (n = 18; 90%) agreed that primary care providers will play a major role in delivering genomic services. Providers indicated that referents' (other providers) opinions about genomic services may affect their decisions about whether to utilize genomic services (normative beliefs). However, most providers (n = 17; 85%) raised concerns about the impact of using genomic services on the process of care (control beliefs). Participants indicated that additional training for providers and patients, and decision support will facilitate the delivery of genomic services (control beliefs). Providers also identified three external barriers: first, uncertainty about genomic findings; second, coordination of care between primary care, specialists and genetic services (system level barriers); and third ethical issues associated with genomic information and services. CONCLUSION: Our findings highlight several opportunities and challenges related to the delivery of genomic medicine at the VHA. The results suggest that strategies to address providers' concerns in the control beliefs domain may be necessary to enhance providers' utilization of genomic services in clinical practice.

Genome-wide linkage scans for type 2 diabetes mellitus in four ethnically diverse populations-significant evidence for linkage on chromosome 4q in African Americans: the Family Investigation of Nephropathy and Diabetes Research Group.

BACKGROUND: Previous studies have shown that in addition to environmental influences, type 2 diabetes mellitus (T2DM) has a strong genetic component. The goal of the current study is to identify regions of linkage for T2DM in ethnically diverse populations. METHODS: Phenotypic and genotypic data were obtained from African American (AA; total number of individuals [N] = 1004), American Indian (AI; N = 883), European American (EA; N = 537), and Mexican American (MA; N = 1634) individuals from the Family Investigation of Nephropathy and Diabetes. Non-parametric linkage analysis, using an average of 4404 SNPs, was performed in relative pairs affected with T2DM in each ethnic group. In addition, family-based tests were performed to detect association with T2DM. RESULTS: Statistically significant evidence for linkage was observed on chromosome 4q21.1 (LOD = 3.13; genome-wide p = 0.04) in AA. In addition, a total of 11 regions showed suggestive evidence for linkage (estimated at LOD > 1.71), with the highest LOD scores on chromosomes 12q21.31 (LOD = 2.02) and 22q12.3 (LOD = 2.38) in AA, 2p11.1 (LOD = 2.23) in AI, 6p12.3 (LOD = 2.77) in EA, and 13q21.1 (LOD = . 2.24) in MA. While no region overlapped across all ethnic groups, at least five loci showing LOD > 1.71 have been identified in previously published studies. CONCLUSIONS: The results from this study provide evidence for the presence of genes affecting T2DM on chromosomes 4q, 12q, and 22q in AA; 6p in EA; 2p in AI; and 13q in MA. The strong evidence for linkage on chromosome 4q in AA provides important information given the paucity of diabetes genetic studies in this population.

Evaluation of gremlin 1 (GREM1) as a candidate susceptibility gene for albuminuria-related traits in Mexican Americans with type 2 diabetes mellitus.

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.

Evaluation of polymorphisms in paraoxonase 2 (PON2) gene and their association with cardiovascular-renal disease risk in Mexican Americans.

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.

The 27-bp repeat polymorphism in intron 4 (27 bp-VNTR) of endothelial nitric oxide synthase (eNOS) gene is associated with albumin to creatinine ratio in Mexican Americans.

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.

Genetics of variation in serum uric acid and cardiovascular risk factors in Mexican Americans.

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.

Genetic variants in the renin-angiotensin system genes are associated with cardiovascular-renal-related risk factors in Mexican Americans.

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.

Heritability of the severity of diabetic retinopathy: the FIND-Eye study.

PURPOSE: Diabetic retinopathy (DR) and diabetic nephropathy (DN) are serious microvascular complications of diabetes mellitus. Correlations between severity of DR and DN and computed heritability estimates for DR were determined in a large, multiethnic sample of diabetic families. The hypothesis was that (1) the severity of DR correlates with the presence and severity of nephropathy in individuals with diabetes mellitus, and (2) the severity of DR is under significant familial influence in members of multiplex diabetic families. METHODS: The Family Investigation of Nephropathy and Diabetes (FIND) was designed to evaluate the genetic basis of DN in American Indians, European Americans, African Americans, and Mexican Americans. FIND enrolled probands with advanced DN, along with their diabetic siblings who were concordant and discordant for nephropathy. These diabetic family members were invited to participate in the FIND-Eye study to determine whether inherited factors underlie susceptibility to DR and its severity. FIND-Eye participants underwent eye examinations and had fundus photographs taken. The severity of DR was graded by using the Early Treatment Diabetic Retinopathy Study Classification (ETDRS). Sib-sib correlations were calculated with the SAGE 5.0 program FCOR, to estimate heritability of retinopathy severity. RESULTS: This report summarizes the results for the first 2368 diabetic subjects from 767 families enrolled in FIND-Eye; nearly 50% were Mexican American, the largest single ethnicity within FIND. The overall prevalence of DR was high; 33.4% had proliferative DR; 7.5%, 22.8%, and 9.5% had severe, moderate, and mild nonproliferative DR, respectively; 26.6% had no DR. The severity of DR was significantly associated with severity of DN, both by phenotypic category and by increasing serum creatinine concentration (chi(2) = 658.14, df = 20; P < 0.0001). The sib-sib correlation for DR severity was 0.1358 in the total sample and 0.1224 when limited to the Mexican-American sample. Broad sense heritabilities for DR were 27% overall and 24% in Mexican-American families. The polygenic heritability of liability for proliferative DR approximated 25% in this FIND-Eye sample. CONCLUSIONS: These data confirm that the severity of DR parallels the presence and severity of nephropathy in individuals with diabetes mellitus. The severity of DR in members of multiplex diabetic families appears to have a significant familial connection.

Endothelial nitric oxide synthase (eNOS) gene polymorphisms and their association with type 2 diabetes-related traits in Mexican Americans.

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.

A genome-wide search for linkage to chronic kidney disease in a community-based sample: the SAFHS.

BACKGROUND: Chronic kidney disease (CKD) phenotypes such as albuminuria measured by urinary albumin creatinine ratio (ACR), elevated serum creatinine (SrCr) and/or decreased creatinine clearance (CrCl) and glomerular filtration rate (eGFR) are major risk factors for renal and cardiovascular diseases. Epidemiological studies have reported that CKD phenotypes cluster in families suggesting a genetic predisposition. However, studies reporting chromosomal regions influencing CKD are very limited. Therefore, the purpose of this study is to identify susceptible chromosomal regions for CKD phenotypes in Mexican American families enrolled in the San Antonio Family Heart Study (SAFHS). METHODS: We used the variance components decomposition approach (implemented in the software package SOLAR) to perform linkage analysis on 848 participants from 26 families. A total of 417 microsatellite markers were genotyped at an average interval of 10 cM spanning 22 autosomal chromosomes. RESULTS: All phenotypes were measured by standard procedures. Mean +/- SD values of ACR, SrCr, CrCl and eGFR were 0.06 +/- 0.38, 0.85 +/- 0.72 mg/dl, 129.85 +/- 50.37 ml/min and 99.18 +/- 25.69 ml/min/1.73 m(2) body surface area, respectively. All four CKD phenotypes exhibited significant heritabilities (P < 0.0001). A genome-wide scan showed linkage on chromosome 2p25 for SrCr, CrCl and eGFR. Significant linkage was also detected on chromosome 9q21 for eGFR [logarithm of the odds (LOD) score = 3.87, P = 0.00005] and SrCr (LOD score = 2.6, P = 0.00026). ACR revealed suggestive evidence for linkage to a region on chromosome 20q12 (LOD score = 2.93, P = 0.00020). CONCLUSION: Findings indicate that chromosomal regions 2p25, 9q21 and 20q12 may have functional relevance to CKD phenotypes in Mexican Americans.

A group randomized trial of a complexity-based organizational intervention to improve risk factors for diabetes complications in primary care settings: study protocol.

BACKGROUND: Most patients with type 2 diabetes have suboptimal control of their glucose, blood pressure (BP), and lipids - three risk factors for diabetes complications. Although the chronic care model (CCM) provides a roadmap for improving these outcomes, developing theoretically sound implementation strategies that will work across diverse primary care settings has been challenging. One explanation for this difficulty may be that most strategies do not account for the complex adaptive system (CAS) characteristics of the primary care setting. A CAS is comprised of individuals who can learn, interconnect, self-organize, and interact with their environment in a way that demonstrates non-linear dynamic behavior. One implementation strategy that may be used to leverage these properties is practice facilitation (PF). PF creates time for learning and reflection by members of the team in each clinic, improves their communication, and promotes an individualized approach to implement a strategy to improve patient outcomes. SPECIFIC OBJECTIVES: The specific objectives of this protocol are to: evaluate the effectiveness and sustainability of PF to improve risk factor control in patients with type 2 diabetes across a variety of primary care settings; assess the implementation of the CCM in response to the intervention; examine the relationship between communication within the practice team and the implementation of the CCM; and determine the cost of the intervention both from the perspective of the organization conducting the PF intervention and from the perspective of the primary care practice. INTERVENTION: The study will be a group randomized trial conducted in 40 primary care clinics. Data will be collected on all clinics, with 60 patients in each clinic, using a multi-method assessment process at baseline, 12, and 24 months. The intervention, PF, will consist of a series of practice improvement team meetings led by trained facilitators over 12 months. Primary hypotheses will be tested with 12-month outcome data. Sustainability of the intervention will be tested using 24 month data. Insights gained will be included in a delayed intervention conducted in control practices and evaluated in a pre-post design. PRIMARY AND SECONDARY OUTCOMES: To test hypotheses, the unit of randomization will be the clinic. The unit of analysis will be the repeated measure of each risk factor for each patient, nested within the clinic. The repeated measure of glycosylated hemoglobin A1c will be the primary outcome, with BP and Low Density Lipoprotein (LDL) cholesterol as secondary outcomes. To study change in risk factor level, a hierarchical or random effect model will be used to account for the nesting of repeated measurement of risk factor within patients and patients within clinics.