Evaluation of the ability of clinical research participants to comprehend informed consent form

BackgroundThe comprehension of informed consent is an integral part of clinical trials. Though India is rapidly becoming a hub of clinical trials very few studies have dealt with the issue of comprehension of informed consent by the patients participating in these trials.MethodsPatients who were invited to participate in a phase 3 multicentric trial of a novel lipid lowering agent were evaluated for comprehension score. The participants were explained about the structured consent form which included the question on background details for the study, design of the study, rights of the patients and miscellaneous aspects pertinent to the clinical trial. The questionnaire comprised of 24 items and each correct answer was assigned a score of 1. Total comprehension score (CS) was obtained by summing all the scores.ResultsParticipants were from diverse socio economic and educational backgrounds. The mean ± SD CS achieved by the participants was 13.4 ± 2.9; median 14(6 to 20). The highest correct responses were obtained for questions on background details (38%). For most of the categories the mean CS was more than 50%. Aspects related to design were mostly difficult to comprehend. No significant difference in the CS was noted between participants from different educational and socioeconomic groups. 8 patients refused to give consent, fear of adverse drug reactions (n = 3) and inability to follow up (n = 5) were the reasons cited by the patients.ConclusionIn conclusion, CS of patients in trials conducted in developing countries can be reasonably good if the investigators explain the consent form in simple language to the participants and CS is not related to the educational status of the participants. Moreover, though a larger majority of patients agree to participate after knowing study details, some patients exercise their right to refuse.     

Evaluating the quality of information about alternatives to research participation in oncology consent forms

A careful consideration of the alternatives to research participation is an essential element of making an informed choice to enroll in a biomedical research study. While there is general agreement on the importance of informing prospective subjects about alternatives to research participation, little is known about how investigators communicate this information. The purpose of this study was to attempt to assess the quality of information about alternatives contained in informed consent documents in oncology randomized controlled trials. Our study indicates that there is room for improvement concerning the discussion of alternatives to research participation in informed consent documents in oncology randomized controlled trials. Though most of the documents in our study met the minimal disclosure standard found in the U.S. federal regulations, less than a third met the reasonable person standard, a widely accepted principle endorsed by the common law and various ethics guidelines and documents. There was a statistically significant difference between the alternative discussions in local and model forms (P < 0.0014). The alternatives discussions in local informed consent documents were more likely to receive higher scores than those in model consent documents, with an odds-ratio of 3.5 to 1.     

Effectiveness of a writing improvement intervention program on the readability of the research informed consent document.

BACKGROUND: Problems with the comprehensibility of human research informed consent have been documented since the 1970s, and efforts aimed at rewriting consents have not been successful in consistently producing more readable consents. This study employed researched principles of reading comprehension research to create writing intervention program designed to help the research writer produce more comprehensible informed consent documents. The purpose of this study was to determine if this intervention program was effective. METHOD: The key component of the writing improvement intervention packet was a newly formatted consent form that contained annotated instructions for researchers on how to write each section for optimum comprehension. The resulting consent forms were evaluated using a Readability and Processability Form (RPF). The RPF is based on reading research and includes the Fry Scale, which yields an approximate grade reading level. The RPF assigned points to each of the 20 areas of comprehension analysis according to strict scoring criteria, and target scores were established by the authors in consultation with the hospital institutional review board. RESULTS: We evaluated 66 post-intervention informed consents. The mean readability and processability score was 62, resulting in the RPF classification of "good." The established readability and processability target range was good to excellent or 61-100 points; 66% of the forms scored in this range. In our 1995 pre-intervention study, the corresponding score was 12%. The target range for grade reading level was 8th grade: 53% scored in that range as compared with 4% in 1995. A question-by-question analysis of each of the 20 checklist items on the RPF identified important aspects of the consent writing that improved and others that were still weak and needed improvement. CONCLUSIONS: The Hartford Hospital writing improvement intervention program was associated with the production of more comprehensible informed consent documents. Using the intervention materials, investigators from a variety of departments could function independently to produce readable consent forms. This program may help others who wish to assist their research departments in creating consents that are written for optimal reading comprehension.     

Comparison of a theory-based (AIDS Risk Reduction Model) cognitive behavioral intervention versus enhanced counseling for abused ethnic minority adolescent women on infection with sexually transmitted infection: results of a randomized controlled trial

BackgroundEthnic minority adolescent women with a history of sexual or physical abuse and sexually transmitted infections represent a vulnerable population at risk for HIV. Community-based interventions for behavior modification and subsequent risk reduction have not been effective among these women.ObjectivesTo evaluate the effects of a theory-based (AIDS Risk Reduction Model) cognitive behavioral intervention model versus enhanced counseling for abused ethnic minority adolescent women on infection with sexually transmitted infection at 6 and 12 months follow-up.DesignControlled randomized trial with longitudinal follow-up.SettingsSouthwestern United States, Metropolitan community-based clinic.ParticipantsMexican-and-African American adolescent women aged 14–18 years with a history of abuse or sexually transmitted infection seeking sexual health care.MethodsExtensive preliminary study for intervention development was conducted including individual interviews, focus groups, secondary data analysis, pre-testing and feasibility testing for modification of an evidence-based intervention prior to testing in the randomized controlled trial. Following informed consents for participation in the trial, detailed interviews concerning demographics, abuse history, sexual risk behavior, sexual health and physical exams were obtained. Randomization into either control or intervention groups was conducted. Intervention participants received workshop, support group and individual counseling sessions. Control participants received abuse and enhanced clinical counseling. Follow-up including detailed interview and physical exam was conducted at 6 and 12 months following study entry to assess for infection. Intention to treat analysis was conducted to assess intervention effects using chi-square and multiple regression models.Results409 Mexican-(n = 342) and African-(n = 67) American adolescent women with abuse and sexually transmitted infection histories were enrolled; 90% intervention group attendance; longitudinal follow-up at 6 (93%) and 12 (94%) months. Intervention (n = 199) versus control (n = 210) group participants experienced fewer infections at 0–6 (0% versus 6.6%, p = .001), 6–12 (3.6% versus 7.8%, p = .005, CI 95% lower-upper .001–.386) and 0–12 (4.8% versus 13.2%, p = .002, CI 95% lower-upper, .002–.531) month intervals.ConclusionsA cognitive behavioral intervention specifically designed for ethnic minority adolescent women with a history of abuse and sexually transmitted infection was effective for prevention of infection. These results provide evidence for development of evidence-based interventions for sexually transmitted infection/HIV. Implications include translation to community-clinic-based settings for prevention of adverse outcomes regarding sexual health of adolescent women.     

Characteristics associated with informed consent for genetic studies in the ACCORD trial

BackgroundPrior studies found that some groups have lower genetic consent rates than others. Participant consent for genetic studies enables randomized trials to examine effects of interventions compared to control in participants with different genotypes.MethodsUnadjusted and multivariate associations between genetic consent rates and participant, study, and consent characteristics in 9573 participants approached for genetics consent in the multicenter Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, which used a layered genetics consent.ResultsEighty-nine percent of eligible participants consented to genetic studies (“Any Consent”) and 64.7% consented to studies of any genes by any investigator (“Full Consent”), with similar rates in randomized groups. Controlling for multiple characteristics, African-Americans had lower consent rates than others (Any Consent Odds Ratio, OR = 0.62, p = 0.0004; Full Consent OR = 0.67, p < 0.0001). Those with high school or higher education level had higher rates than less than high school graduates (Full Consent ORs 1.41–1.69, p-values < 0.0001). Consent rates were lower when genetics consent was separate from the main trial consent on the same day (Any Consent OR 0.30; Full Consent OR 0.52, p values < 0.0001) or on a subsequent day (Any Consent OR 0.70, p = 0.0022; Full Consent OR 0.76, p = 0.0002).ConclusionHigh rates of consent for genetic studies can be obtained in complex randomized trials, with lower consent rates in African-Americans, in participants with less than high-school education, and for sharing samples with other investigators. A genetics consent separated from the main trial consent was associated with lower consent rates.     

Effectiveness of automated notification and customer service call centers for timely and accurate reporting of critical values: A laboratory medicine best practices systematic review and meta-analysis

ObjectiveTo conduct a systematic review of the evidence available in support of automated notification methods and call centers and to acknowledge other considerations in making evidence-based recommendations for best practices in improving the timeliness and accuracy of critical value reporting.Design and methodsThis review followed the Laboratory Medicine Best Practices (LMBP) review methods (Christenson, et al. 2011). A broad literature search and call for unpublished submissions returned 196 bibliographic records which were screened for eligibility. 41 studies were retrieved. Of these, 4 contained credible evidence for the timeliness and accuracy of automatic notification systems and 5 provided credible evidence for call centers for communicating critical value information in in-patient care settings.ResultsStudies reporting improvement from implementing automated notification findings report mean differences and were standardized using the standard difference in means (d = 0.42; 95% CI = 0.2–0.62) while studies reporting improvement from implementing call centers generally reported criterion referenced findings and were standardized using odds ratios (OR = 22.1; 95% CI = 17.1–28.6).ConclusionsThe evidence, although suggestive, is not sufficient to make an LMBP recommendation for or against using automated notification systems as a best practice to improve the timeliness of critical value reporting in an in-patient care setting. Call centers, however, are effective in improving the timeliness of critical value reporting in an in-patient care setting, and meet LMBP criteria to be recommended as an “evidence-based best practice.”DisclaimerThe findings and conclusions in this article are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention/Agency for Toxic Substances and Disease Registry (CDC/ATSDR).     

Method development for routine liquid chromatography-mass spectrometry measurement of the alcohol biomarker phosphatidylethanol (PEth) in blood

BackgroundPhosphatidylethanol (PEth) is a group of phospholipids formed from ethanol and phosphatidylcholine by action of phospholipase D. Measurement of PEth in whole blood samples is employed as an alcohol biomarker. This work aimed to further develop an LC–MS method for PEth to make it practical for routine laboratory use.MethodsBlood samples were obtained from blood donors and from the clinical samples pool. A whole blood total lipid extract was separated on a C4 column, followed by ESI-MS detection of the deprotonated molecules in SIM mode or ESI-MS/MS detection of the major product ions (fatty acid fragments) by SRM.ResultsInitial results indicated that individual calibration curves are required for MS quantitation of some PEth forms, and that deuterated analogs are preferable over phosphatidylpropanol as the internal standard. PEth-16:0/18:1 was the single most sensitive molecular form as alcohol biomarker, being detected in every of 211 blood specimens containing 0.1–20 μmol/L total PEth at reporting limits in the range 0.1–1.0 μmol/L. PEth-16:0/18:1 and 16:0/18:2, accounting for about 36% and 26%, respectively, of the total amount, correlated well with total PEth (R² = 0.922–0.940), but the correlation was better for the sum of both forms (R² = 0.994). Based on analysis of specimens from 200 blood donors, 95% reference intervals (CLSI C28-A3) were estimated to be < 0.70 μmol/L for total PEth, < 0.20 μmol/L for PEth-16:0/18:1, and < 0.18 μmol/L for PEth-16:0/18:2.ConclusionsThe LC-ESI-MS(/MS) method allowed for simultaneous qualitative and quantitative measurements of PEth forms in whole blood samples. Related to the routine application of blood PEth as alcohol biomarker, reference intervals were suggested for total PEth and the major molecular forms PEth-16:0/18:1 and 16:0/18:2.     

A brief assessment of capacity to consent instrument in acutely intoxicated emergency department patients

Objective

The aim of this study was to determine to what extent acute alcohol intoxication effects capacity to assent, consent, or refuse research participation.

Elevated levels of myeloperoxidase, white blood cell count and 3-chlorotyrosine in Taiwanese patients with acute myocardial infarction

ObjectivesInflammation, a major risk factor for acute myocardial infarction (AMI), is associated with leukocytic activation, secretion of myeloperoxidase (MPO) and generation of the oxidative damage marker, 3-chlorotyrosine (3-Cl-Tyr). To study their association with AMI and their value in diagnosis of AMI, white blood cell (WBC) count, plasma MPO, plasma 3-Cl-Tyr, and conventional risk factors such as cardiac troponin I and CK-MB were examined in AMI patients during the onset of chest pain.MethodsAfter obtaining informed consent, blood samples were collected from 77 AMI patients during the onset of chest pain and from 53 normal controls. The samples were analyzed for WBC count using SE-9000 automated analyzer. Plasma MPO was measured by an enzyme-linked immunosorbent assay. Plasma levels of 3-Cl-Tyr, a product of MPO, were analyzed by HPLC coupled with Coularray electrochemical detection.ResultsThe WBC, plasma MPO and 3-Cl-Tyr levels were significantly elevated in AMI patients than in normal controls (p < 0.001). The levels of WBC, MPO and 3-Cl-Tyr alone were strongly associated with the prevalence of AMI. Plasma MPO was correlated with 3-Cl-Tyr (r = 0.389, p < 0.01) and WBC counts (r = 0.405, p < 0.01) respectively. The ROC curve analyses suggested that MPO had the best specificity and sensitivity among these oxidative stress-related markers.ConclusionPlasma MPO value should be considered as a better marker for early diagnosis of AMI, as compared with WBC count or 3-Cl-Tyr.     

Cognitive behavioural therapy as an adjunct to pharmacotherapy for treatment resistant depression in primary care: the CoBalT randomised controlled trial protocol

BackgroundAntidepressants are often the first-line treatment for depression but only one third of patients respond fully to pharmacotherapy. This paper describes the protocol for a randomised controlled trial (RCT) designed to evaluate the clinical and cost effectiveness of cognitive behavioural therapy (CBT) as an adjunct to pharmacotherapy for patients with treatment resistant depression in primary care.Methods/designCoBalT is a two parallel group multi-centre pragmatic RCT. Eligible participants were those who: (i) were aged 18–75 years; (ii) were currently taking antidepressant medication (for at least 6 weeks at an adequate dose); (iii) scored ≥ 14 on the Beck Depression Inventory (BDI-II); (iv) had adhered to their medication; and (v) met ICD-10 criteria for depression (assessed using the Clinical Interview Schedule — revised version). Those who gave written informed consent were randomised to one of two treatment groups: usual care or usual care plus CBT. The primary outcome is depressive symptoms assessed using the BDI-II at 6 months post-randomisation. Secondary outcomes measured at 6 and 12 months include quality of life, antidepressant use and health care utilisation. Outcomes will be analysed on an intention-to-treat basis.DiscussionThe CoBalT trial will provide evidence on the clinical and cost effectiveness of CBT as an adjunct to antidepressant medication in the treatment of depression that has not responded to pharmacotherapy. Given the move to widen access to ‘talking therapies’, the results of this study will be timely.     

Usefulness of a run-in period to reduce drop-outs in a randomized controlled trial of a behavioral intervention

ObjectivesWe evaluated the usefulness of a simple run-in period to reduce drop-outs in a behavioral intervention to improve blood pressure (BP). In a pilot study where a run-in period was not used, we had a 25% drop-out rate.MethodsA prospective evaluation was performed in the context of a blinded 3-arm randomized trial. Participants are eligible if they have uncontrolled BP on 2 consecutive visits. Potential participants are approached during a routine visit, informed, consented and enrolled. After a 1-month run-in period during which all participants receive a phone call to: i) verify phone availability, ii) get basic information on treatment, and iii) confirm the baseline visit, participants return for a baseline visit. They are then randomized to one of the three treatment arms: usual care, non-tailored counseling, or tailored counseling. Participants make return visits at 3, 6 and 12 months.ResultsOf the 1275 potential participants who received detailed study information, 301 consented to participate, of whom 226 were enrolled. During the run-in period, 73 withdrew consent and 153 participants were randomized; 7 subsequently dropped out. There were no differences (p > .1) between the 73 cancelled and the 153 randomized patients. There were fewer drop-outs than in the pilot study (5% vs. 25%, p < .0001).ConclusionsThe run-in period reduces the number of drop-outs after randomization and improves statistical power. In order to retain external validity, it is important to compare participants who remain in the study and those that cancel, and incorporate that in generalizing from the study.     

Rationale, study design and sample characteristics of a randomized controlled trial of directly administered antiretroviral therapy for HIV-infected prisoners transitioning to the community - a potential conduit to improved HIV treatment outcomes

BackgroundHIV-infected prisoners experience poor HIV treatment outcomes post-release. Directly administered antiretroviral therapy (DAART) is a CDC-designated, evidence-based adherence intervention for drug users, yet untested among released prisoners.MethodsSentenced HIV-infected prisoners on antiretroviral therapy (ART) and returning to New Haven or Hartford, Connecticut were recruited and randomized 2:1 to a prospective controlled trial (RCT) of 6 months of DAART versus self-administered therapy (SAT); all subjects received case management services. Subjects meeting DSM-IV criteria for opioid dependence were offered immediate medication-assisted treatment. Trained outreach workers provided DAART once-daily, seven days per week, including behavioral skills training during the last intervention month. Both study groups were assessed for 6 months after the intervention period. Assessments occurred within 90 days pre-release (baseline), day of release, and then monthly for 12 months. Viral load (VL) and CD4 testing was conducted baseline and quarterly; genotypic resistance testing was conducted at baseline, 6 and 12 months. The primary outcome was pre-defined as viral suppression (VL < 400 copies/mL) at 6 months.ResultsBetween 2004 and 2009, 279 participants were screened, of which 202 met eligibility criteria and 154 were ultimately enrolled in the study; 103 subjects were randomized to DAART and 51 to SAT. Subjects were mostly male (81.2%), people of color (87.0%), had an alcohol use disorder (39.7%), had underlying depression (54.2%), were virally suppressed (78.8%) and had a mean CD4 = 390.7 cells/mL.ConclusionsOutcomes from this RCT will contribute greatly to HIV treatment outcomes after release from prison, a period associated with adverse HIV and other medical consequences.     

Predictors of recruited melanoma families into a behavioral intervention project

BackgroundExamination of families represents an important priority in health research. In this paper we report on individual and family-level factors associated with enrollment in a cancer prevention research project. We approached families affected by melanoma for possible participation in a randomized controlled trial of a web-based communication and support intervention.MethodsWe recruited three family members per family for assessment — the melanoma case, a first-degree relative (FDR), and a relative who is a parent of a child age 18 or younger. Recruitment involved three steps: requesting the physician's consent to approach the melanoma case, approaching the case to request their participation and family contact information, and they approaching the FDRs and parents.ResultsOf the 1380 families approached, 313 were enrolled, 263 were excluded because we could not find or contact a family member (FDR or parent), 331 did not have eligible family members, and 473 refused. The most frequently noted reason for refusal was being too busy or having no time. The primary predictors of participation for cases (OR = 1.6; CI = 1.01–2.51) and FDRs (OR = 2.15; CI = 1.11–4.13) included higher educational attainment. FDRs were more likely to enroll if they were female (OR = 1.77; CI = 1.1–.85) and parents were more likely to enroll if the case had been diagnosed more recently (OR = 3.3; CI = 1.9–5.93), if the parent was partnered (OR = 4.37; CI = 1.86–10.26), and if the parent lived in the same city as the case (OR = 2.88; CI = 1.08–7.68).ConclusionsThe results can provide information on potential directions for future family recruitment.     

Validation of the Taiwanese version of the Athens Insomnia Scale and assessment of insomnia in Taiwanese cancer patients

ContextIt is well known that insomnia is highly prevalent in cancer patients. Although various studies have used the Athens Insomnia Scale (AIS) for insomnia assessment, it has never been applied to cancer patients with insomnia.ObjectivesThe purpose of this study was to establish the reliability and validity of the Taiwanese AIS version (AIS-T) and evaluate the severity of insomnia among cancer patients in Taiwan.MethodsUsing a cross-sectional research design, 195 cancer patients (n = 195) were recruited from outpatient oncology clinics.ResultsCronbach’s alpha for internal consistency was 0.83, and the test-retest reliability was 0.94 over an interval of three days, based on a sample of 30 patients. Moreover, concurrent validity could be evaluated by significant correlations of the AIS-T with the Pittsburgh Sleep Quality Index-Taiwan form (PSQI-T) (r = 0.82, P < 0.001) and sleep efficiency measured by Actiwatch parameters (r = ?0.54, P < 0.001). Construct validity could be established by the Brief Fatigue Inventory-Taiwan form (r = 0.56, P < 0.001) and Medical Outcomes Study Short Form-36-Taiwanese version (physical component summary: r = ?0.52, P < 0.001; mental component summary: r = ?0.53, P < 0.001). The AIS-T could detect significant known-group validity from sleep quality (PSQI-T ≥5 or <5, respectively). The Actiwatch parameters are consistent with the results of the AIS-T, and both data sets indicate that patients experienced sleep disturbances. The prevalence of insomnia, as defined by the criteria of the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders, 4th ed., was 22.56%; 49.2% subjects had significant insomnia at the score ≥6 at AIS-T.ConclusionThis study concludes that the AIS-T is a reliable and valid instrument for assessing insomnia among cancer patients in Taiwan.     

Analysis of glucagon-like peptide 1; what to measure?

BackgroundGlucagon-like peptide 1 (GLP-1) is a gut hormone which acts as an incretin and is therefore of major interest in treatment of type II diabetes mellitus. GLP-1 circulates in many different forms, some of which are biologically active and others are not. Our hypothesis was that various methods to measure GLP-1 detect different forms of GLP-1, which may cause confusion when comparing results.MethodsWe compared three assays, the GLP-1 (active) ELISA (Linco research; ELISA_LINCO), GLP-1 (total) RIA (Linco research; RIA_LINCO) and the total GLP-1 RIA developed by the group of Holst (RIA_HOLST) on specimens obtained during meal studies. In addition, we studied the effect of addition of a DPP-4 inhibitor.ResultsThe correlation between RIA_LINCO and ELISA_LINCO was highest (r = 0.76; n = 35; p < 0.01), whereas results of RIA_HOLST correlated less with those of RIA_LINCO and ELISA_LINCO (r = 0.35 and 0.39 respectively; n = 35; p < 0.05). GLP-1 results measured with ELISA_LINCO were higher (median 28%; p < 0.001) upon addition of the DPP-4 inhibitor.ConclusionTwo commercially available GLP-1 assays do not necessarily give results equal to the well-defined GLP-1 assay developed in Copenhagen. Absolute values are also different due to differences in standardisation. Moreover, assays detect different forms of GLP-1, which hampers comparison to published data.     

Managing patient flow with triage streaming to identify patients for Dutch emergency nurse practitioners

IntroductionWe developed a stream system to the current triangle system in order to manage patient flow at the emergency department and to clarify ENP role boundaries.MethodsData on admission and death rates – indicating injury severity – and data on length of stay – indicating resource utilisation – were collected from 48,397 patients triaged in the Netherlands in 2009.ResultsA total of 24,294 (50.2%) patients were triaged as ‘suitable for treatment by an ENP’ (ENP-stream). Remaining patients were triaged ‘medium care’ or ‘high care’. In the medium and high care groups, significantly more admissions took place (6100, 25.3%) and significantly more patients died (31, 0.1%) compared to the patient group in the ENP-stream (admissions: 840, 3.5%, p < 0.001 and deaths 0, 0.0%, p < 0.001). The ENP-streaming is an accurate predictor of not needing to be admitted (PPV = 97%) and of ED survival (PPV = 100%). Mean length of stay was significantly shorter for patients in the ENP-stream compared to the other patients (back transformed values: 74 vs. 147 min, p < 0.001).ConclusionThis study showed excellent correlation between the ENP-streaming and patients’ injury severity and resource utilisation, suggesting high internal validity of our triage streaming system. It clarifies the ENP role, minimising the subjectivity of patient allocation.     

A comparison of restriction fragment length polymorphism, tetra primer amplification refractory mutation system PCR and unlabeled probe melting analysis for LTA+252 C>T SNP genotyping

BackgroundFrom the wide range of methods currently available for genotyping, we wished to identify a quick, reliable and affordable approach for routine use in our laboratory for LTA + 252 C > T SNP screening.MethodsWe set up and compared three genotyping methods for SNP detection: restriction fragment length polymorphism (RFLP), tetra primer amplification refractory mutation system PCR (TPAP) and unlabeled probe melting analysis (UPMA). The SNP model used was LTA + 252 C > T, a cytokine gene polymorphism that has been associated with response to treatment in rheumatoid arthritis. The study was performed using 46 samples from healthy Caucasian volunteers.ResultsAllele and genotype distribution was similar to that previously described in the same population. All three genotyping methods showed good reproducibility and are suitable for a medium scale throughput molecular platform. UPMA was the most cost effective, reliable and safe method since it required the shortest technician time, could be performed in a single closed tube and involved automatic data analysis.ConclusionThis work is the first to compare these three genotyping techniques and provides evidence for UPMA being the method of choice for LTA + 252 C > T SNP genotyping.     

Association of exonic variants of Klotho with metabolic syndrome in Asian Indians

BackgroundKlotho, an anti-aging gene, is a functional candidate for metabolic syndrome. We conducted a cross-sectional study to evaluate the association of the genetic variants of Klotho with metabolic syndrome and surrogates of insulin resistance in Asian Indians.MethodsWe recruited 428 clinically normal subjects for the study. Genotyping was done by polymerase chain reaction and restriction fragment length polymorphism.ResultsSignificant and borderline associations of the KL-VS (OR = 15.88 [95%CI, 2.56–98.70], p = 0.003) and C1818T (OR = 0.28 [95%CI, 0.07–1.07], p = 0.063) variants of the Klotho gene, respectively, were observed with metabolic syndrome. The association of the KL-VS variant with metabolic syndrome could be linked to its observed influence on high blood glucose (OR = 6.92 [95% CI = 1.75–27.44], p = 0.006), high blood pressure (OR = 5.21 [95%CI = 1.00–38.43], p = 0.046), insulin resistance (OR = 3.59, [95%CI = 1.01–12.79], p = 0.048) and trend towards its association with hypertriglyceridemia (OR = 3.69 [95%CI = 0.92–14.77], p = 0.065).ConclusionsThe genetic variants of Klotho might predict risk for metabolic syndrome and insulin resistance in Asian Indians. However, larger studies in other ethnic populations are warranted to determine the role of these gene variants in the etiology of metabolic syndrome.