First-degree Relatives Of Patients Research Articles

Empowering Family Glaucoma Risk Communication Using QR-Code-Mediated Online Intervention

Attempts at engaging relatives of glaucoma patients in education and screening have had limited success. This study explores the feasibility of an electronic intervention to facilitate direct yet reliable glaucoma risk communication between open-angle glaucoma patients (probands) and their first-degree relatives (FDRs). Prospective survey and assessment of intervention. Fifty adult probands, engaging 140 FDRs. Phase I was an iterative process involving creating a customized website and Quick Response (QR)-code-based intervention designed with input from probands, FDRs of patients, community members, and researchers. In phase II, the intervention was deployed in a clinical setting; this involved recruiting probands who had a smartphone and were willing to use the QR-code to message their FDRs a standard message, including a website link about glaucoma risk in FDRs and the importance of getting examined. Follow-up interviews were conducted with probands 1 to 2 weeks after their clinic visit to assess the impact of the intervention. Demographic data, website analytics, and participant feedback were collected and analyzed. Increased awareness of glaucoma risk among FDRs and enhanced discussions. At the time of the first interview, probands reported that 70% of the FDRs were aware of the probands' glaucoma diagnosis, but only 26% had undergone glaucoma screening. Ninety percent of probands had no issues using the QR-codes. Website analytics recorded 73 visits from 51 distinct internet protocol addresses (IPs). After receiving the standard message, 95% of FDRs followed up with the probands, actively discussing glaucoma. Of the probands, 84% completed the follow-up interview 1 to 2 weeks after enrollment. Fifty-nine percent of the FDRs were reported to have scheduled screening appointments. The collected feedback revealed that 96% of probands found the intervention helpful, fostering glaucoma discussions with their FDRs and improving probands' comfort level in discussing health issues with FDRs from baseline (very comfortable: 88%, comfortable: 8%, neutral: 2%, and very uncomfortable: 2%) to the follow-up interview (very comfortable: 98% and comfortable: 2%). This innovative online method of communicating the risk of glaucoma to FDRs of probands prompted and increased the comfort level of familial discussions of glaucoma. More than half of FDRs reported making an appointment to get screened for glaucoma. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

FRI686 Phenotypic Profiling And Molecular Mechanisms In Hyperparathyroidism-jaw Tumor Syndrome

Abstract Disclosure: R. Tora: None. J. Welch: None. J. Sun: None. S.K. Agarwal: None. D.A. Bell: None. M. Merino: None. L.S. Weinstein: None. W.F. Simonds: None. S. Jha: None. Background: Hyperparathyroidism-Jaw Tumor (HPT-JT) syndrome is a heritable form of primary hyperparathyroidism (PHPT) that is associated with tumors in the parathyroid, jaw, kidney, and uterus. We previously presented on the clinical characteristics of primary hyperparathyroidism in our cohort. Methods: We now expand on the report through review of uterine tumors, immunohistochemical staining for parafibromin, sequencing of parathyroid and kidney tumor tissue, and RNA-seq of parathyroid tumors. Results: We identified 68 patients (36 males, 32 females) from 29 kindreds with HPT-JT with median age at last follow-up of 39 [29-53] years. Of these, 7 patients were unaffected (2 males, 5 females). Among females, 12/32 (38%) developed uterine tumors with multiple adenomyomatous polyps, an unusual form of endometrial polyps seen in 10/24 tumors (42%). Given that these types of lesions are very rare in the general population, it is likely that such epithelial-mesenchymal uterine proliferations are a characteristic feature of HPT-JT syndrome.Solid kidney tumors were seen in 4/61 patients (7%). Three had surgery for the tumors - 2/3 were female and had mixed epithelial stromal tumor, while the third patient, a 6-year old male, had metastatic Wilm’s tumor as his initial disease-related manifestation. Among these, two had a germline CDC73 variant at the p.M1 residue while the third patient had the germline variant p.L95P; however, sequencing of his tumor tissue showed a “second hit” at the p.M1 residue resulting in loss of heterozygosity in the tumor. The fourth patient, a female with p.Y55S variant, is being conservatively managed with no kidney surgery yet. All three women with kidney tumors also had a history of uterine tumors. Parafibromin staining of 19 available CDC73 related parathyroid tumors (13 adenomas and 6 carcinoma) did not correlate with histology or genotype. Pathway analysis of 21 parathyroid tumors (8 HPT-JT-related adenomas, 6 HPT-JT-related carcinomas and 7 sporadic parathyroid carcinoma with wild-type CDC73) showed a significant association of HPT-JT-related parathyroid carcinoma with growth, transmembrane receptor protein tyrosine kinase signaling and mesodermal commitment pathways. Conclusion: Multiple, recurrent atypical adenomyomatous uterine polyps appear to be characteristic of HPT-JT syndrome. Our findings support germline testing at a young age in first-degree relatives of patients with HPT-JT given onset of manifestations as early as 6 years. Variants at M1 residue appear to predispose to genitourinary tumors. At present, there are no therapeutic approaches to compensate for CDC73 inactivation. Future research to identify standards of care and therapeutics targets are warranted for this rare disease. Presentation: Friday, June 16, 2023

OC 72.4 Risk of Venous Thromboembolism (VTE) in First-Degree Relatives of Patients with VTE Compared with General Population VTE Risk

OC 72.4 Risk of Venous Thromboembolism (VTE) in First-Degree Relatives of Patients with VTE Compared with General Population VTE Risk

Cognitive impairment in 'non-user' first-degree relatives of persons with cannabis dependence syndrome: A pilot, endophenotype study.

Cannabis use disorders are global emerging problem nowadays, with high prevalence and morbidity. Cognitive impairments, and also corresponding genetic vulnerability, has been fairly replicated in individuals with cannabis dependence. However, there are few studies that assess cognitive functioning as an endophenotype or a trait marker for cannabis dependence. While the primary objective of this study was to assess the endophenotype pattern of cognitive dysfunction in cannabis dependence, assessing the association between the degree of cognitive functioning, and their socio-demographicand clinical variables in the cannabis dependence patients and their first-degree relatives was the secondary objective. We compared cognitive functioning across three groups- patients with cannabis dependence syndrome, their 'non-user' first-degree relatives and healthy controls, with 30 participants in each group. Five cognitive domains- attention and concentration, verbal fluency, memory, visuospatial ability and executive functions were assessed. We assessed for endophenotype pattern of statistical significance in pairwise analyses of Kruskal-Wallis test, which was corrected for multiple comparisons. Subsequently, correlation analysis to assess association of cognitive impairment with socio-demographic and clinical variables was conducted. Although impairment in attention and executive functions also was seen in patients with cannabis dependence, endophenotype pattern of statistical significance in pairwise analyses, with impairment in first-degree relatives too, was seen in all sub-scores of verbal fluency and verbal memory. None of the correlations were significant. 'Non-user' first-degree relatives of patients with cannabis dependence too show significant cognitive impairment. Verbal fluency and verbal memory are possible endophenotypes or trait markers for cannabis dependence syndrome.

Atypical manifestation of celiac disease in carriers of HLA mutant gene

Annotation. Celiac disease is an autoimmune disease, which is manifested by enteropathy of the small intestine and is caused by the consumption of gluten-containing foods. According to statistics, the number of patients suffering from this disease has increased by 7.5% recently, which may be due to epigenetic factors and improvements in diagnostic methods of gluten intolerance. Human Leukocyte Antigen (HLA) gene plays a major role in the pathophysiological development of celiac disease. The function of HLA is an autoimmune response to endogenous and exogenous proteins. The pathogenesis of organ damage is based on an autoimmune reaction that occurs as a result of the entry of gliadin – the main component of gluten – into the organism. The influence of circulating immune complexes (CIC) leads to the appearance of typical and numerous atypical manifestations of the disease. This, in turn, significantly complicates the diagnosis and prescription of the correct treatment, which can ensure the restoration of the structure of the affected organs and improve the quality of life for patients. Atypical manifestations of gluten enteropathy are diverse, including chronic fatigue syndrome, damage to joints, bones, liver, male and female infertility, thyroid gland dysfunction, dermatitis, and tooth enamel structure disorders. Taking into account the importance of this issue, we conducted a systematic review and analysis of sources related to this question. The search was conducted in the scientometric databases PubMed, Google Scholar, Web of Science, Scopus, mostly over the last three years. In particular, it was found that screening for the specific HLA gene in first-degree relatives of patients with gluten enteropathy allows for an explanation of the exact etiology of possible atypical symptoms - manifestations of celiac disease, and subsequently prescribing a gluten-free diet that leads to the involution of the negative impact of the immune system on target organs. Moreover, this screening will be useful for identifying risk groups because manifestations of celiac disease could be in different ages and have different symptoms.

Analysis of MCP-1 Levels and TNF-alfa /Il-10 Ratio in First Degree Relatives (FDR) Type 2 Diabetes Mellitus Subjects with High Fat Diet Treatment

Type 2 diabetes mellitus is a chronic metabolic disease, which involves a variety of pathogenic processes. Overall these processes result in loss of mass and/or function of pancreatic-cells which is manifested as hyperglycemia. The influence of familial factors appears to be involved in the initiation and development of T2DM through both genetic and non-genetic factors. In the same family environment as patients with diabetes, first-degree relatives of patients with diabetes show a 30-70% increased risk of developing diabetes. Insulin resistance and cell dysfunction have been identified in individuals with a family history of diabetes, even before the onset of T2DM symptoms. Monocyte chemoattractant protein-1 (MCP-1) is a CC-chemokine with an attractant effect on monocytes, memory T cells and basophils. Expression of adipose tissue MCP-1 and circulating levels were positively correlated with adiposity. Larger adipocytes are associated with insulin resistance. This study aims to determine the changes in MCP-1 expression on monocytes before and after treatment with a high-fat diet for five days. The results showed that there was a change in inflammatory activity which was indicated by a high ratio of TNF-alfa/IL – 10 in the FDR group so that it could increase MCP-1 activity. However, there was no relationship between serum MCP-1 levels and the percentage of CD14+CD16+ monocytes in both groups.

Macular Pigment Optical Density in First Degree Relatives of Age-Related Macular Degeneration Patients

Purpose To measure the macular pigment optical density in first-degree relatives of patients with age-related macular degeneration and compare it with a healthy control group. Methods One hundred and twenty-eight healthy subjects who were first-degree relatives of age-related macular degeneration patients were included in the study (Group 1). As the control group, 74 healthy subjects were included in the study (Group 2). The right eyes of all cases were included in the study. Macular pigment optical density was measured with a commercially available device (MPSII®, Elektron Technology, Switzerland) using technology based on heterochromatic flicker photometry. Central foveal thickness and subfoveal choroidal thickness were measured with spectral-domain optical coherence tomography. Values were compared between the two groups. Results There were 54 males and 74 females in Group 1 and 32 males and 42 females in Group 2. The mean ± SD ages of Group 1 and Group 2 were 49.0 ± 7.6 and 41.8 ± 8.6, respectively. Mean ± SD macular pigment optical density values of Group 1 and Group 2 were 0.43 ± 0.09 and 0.47 ± 0.12 (p = 0.048), mean ± SD central foveal thickness were 208 ± 19 and 216 ± 8 µm (p = 0.014), and mean ± SD subfoveal choroidal thickness were 232 ± 29 and 250 ± 21 µm (p = 0.002), respectively. Conclusion The macular pigment optical density values were significantly lower in the first-degree relatives of patients with age-related macular degeneration than in the control group. Macular pigment optical density may be a marker for the development of age-related macular degeneration in the future in the first-degree relatives of age-related macular degeneration patients. Further prospective studies with a larger number of participants will be needed to confirm our results moreover, to clarify its benefit as an early diagnostic biomarker.

Adipokine Profile on Joint and Periodontal Conditions in First-degree Relatives of Patients with Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by joint inflammation and destruction. Establish the association between Porphyromonas gingivalis (P. gingivalis) infection, body mass index (BMI), joint involvement, and serum adipokines in first-degree relatives (FDR) of patients with rheumatoid arthritis (RA). The cross-sectional study evaluated 124 FDR and 124 healthy controls (HC). The clinical examination included joint and radiographic evaluation and calculation of BMI. Serum adipokine levels were measured (leptin, vaspin, adiponectin, resistin, and adipsin), as were the erythrocyte sedimentation rate, C-reactive protein, and anti-citrullinated protein antibodies. Investigations were performed to detect P. gingivalis, and anti-P. gingivalis antibodies. Statistical analyses were performed to confirm associations. Leptin levels in FDR were associated with BMI >25 (OR, 2.64; 95%CI, 1.17-5.97; P=0.019), radiographic damage (Simple Erosion Narrowing Score [SENS])/hands, total SENS, and joint space narrowing in feet (P=0.037, 0.026, 0.020, respectively). FDR had more tender joints (P=0.018); this finding was associated with high levels of leptin and resistin and low levels of adipsin (P=0.040, 0.040, and 0.019, respectively). The presence of P. gingivalis was related to FDR, low levels of adipsin, resistin, adiponectin, and a trend toward higher levels of leptin (P=0.002, 0.001, 0.003, and 0.060, respectively), whereas anti-P. gingivalis antibodies were related to low levels of adipsin (P=0.001). In FDR, serum adipokine levels were associated with overweight and the presence of P. gingivalis. Adipokine levels were also associated with joint involvement. Hence, adipokines may be involved in the pathogenesis of RA in FDR and warrant further investigation.

Relationship between health information literacy and health promoting lifestyle among first-degree relatives of patients with colorectal cancer in China: the mediating effect of health belief.

History of first-degree relatives with colorectal cancer is one of the most important and common risk factors for colorectal cancer in China. Most chronic diseases, such as malignancies, are preventable by adopting health-promoting behaviors and other approaches. However, the relationships among factors affecting the health-promoting lifestyles of first-degree relatives with colorectal cancer have not been sufficiently studied. This study aimed to test the mediation effects of Health belief in the relationship between health-promoting lifestyle and health information literacy among first-degree relatives with colorectal cancer. A cross-sectional descriptive design was conducted using convenience sampling of 856 first-degree relatives of CRC patients attending three tertiary care hospitals in Nanchong and Deyang of China from December 2020 to December 2022. Questionnaires were used to collect data on the participants' demographic information, the colorectal cancer health beliefs, the health promotion lifestyle, and the health information literacy. Data were analyzed with descriptive statistics, one-way ANOVA, Pearson's correlation coefficients, and mediation analysis using SPSS 25.0 program and its macro-program PROCESS. The findings indicated health information literacy was less, health belief was at the medium level, and performance of health promotion behavior was average for first-degree relatives of colorectal cancer. Whereas first-degree relatives of colorectal cancer health-promotion lifestyle had a positive correlation with health beliefs (r = 0.376, p < 0.01) and health information literacy (r = 0.533, p < 0.01), health beliefs had a positive correlation with health information literacy (r = 0.337, p < 0.01). Health beliefs mediated the positive effect of health information literacy on health-promoting lifestyles (β =0.420, 95% CI, 0.288-0.581), and indirect effects accounted for 14.0% of the total effect. Health information literacy and health beliefs are key factors associated with a health-promoting lifestyle among first-degree relatives with colorectal cancer. These factors have direct and indirect effects on each other and on health-promoting lifestyles. To enhance health-promoting lifestyles among first-degree relatives with colorectal cancer, interventions that strengthen health beliefs and provide health information literacy should be developed.

OS-116-YI - Inreased risk of hepatocellular carcinoma among first-degree relatives of patients with biopsy-proven NAFLD – a multigenerational nationwide cohort study

OS-116-YI - Inreased risk of hepatocellular carcinoma among first-degree relatives of patients with biopsy-proven NAFLD – a multigenerational nationwide cohort study

Utility of multi-gene panel-based germline analysis following genomic profiling and cascade testing in advanced solid tumors: An initial report of the BRANCH study.

10615 Background: Genetic testing for pathogenic germline variants (PGVs) is performed to identify hereditary cancer syndromes (HCS) and to evaluate the application of targeted therapies in clinical oncology. Multi-gene panels (MGPs) have become popular for identifying HCS; however, their clinical utility in therapeutic applications and confirmatory germline testing for presumed PGVs and in cascade testing are not well established. Methods: BRANCH [UMIN000046085] is a multicenter clinical study to confirm PGVs in: i) patients with advanced solid tumors in whom a presumed PGV has been detected by comprehensive genomic profiling (CGP) (cohort A); ii) patients who received a germline BRCA (gBRCA) test (cohort D); and iii) first-degree relatives of patients with PGVs identified in this study (cohort C). PGVs were examined in 35 HCS genes using an MGP combined with digital multiple-ligation-dependent probe amplification. Results: MGP results were available for 75 patients in cohort A and 83 in cohort D (3 February 2023). The most common cancer in cohort A was colorectal cancer (13%) followed by ovarian (12%) and breast (11%) cancers. Of 103 tested presumed PGVs, 46 (45%) were confirmed as PGVs, with the highest germline conversion rates in BRCA1 (8/8, 100%), followed by PALB2 (5/6, 83%) and BRCA2 (15/19, 79%) among the genes tested in ≥3 patients. In tissue-based CGP, true PGVs had a higher variant allelic frequency (median 55.7% [range, 31.9-96.8]) than non-PGVs (37.0% [9.3-86.9]). In cohort D, 61 (74%) patients had breast cancer, including one with both breast and ovarian cancers. All BRCA PGVs identified by gBRCA test were identified by MGP in 28 BRCA-positive patients. Intriguingly, among 55 patients (66%) in whom no BRCA PGV was detected by gBRCA test, non-BRCA PGVs were identified in 6 (11%) patients (2 PALB2 and 1 each of ATM, CHEK2, MSH2 [large deletion], and TP53). Thirty relatives in 18 pedigrees received MGP-based cascade testing in cohort C. The most frequent target genes were BRCA2 followed by BRCA1 and PALB2. The same PGVs as the probands were confirmed in 11 (37%) individuals and novel PGVs were identified in 2 (7%) relatives, leading to double PGVs in homologous recombination genes ( PALB2+ BRCA2 and BRCA2+ ATM), respectively . Conclusions: MGP successfully determined germline variants among presumed PGVs identified by CGP in patients with advanced solid tumors, and detected non-BRCA PGVs in 10% of gBRCA-negative patients. Furthermore, MGP-based cascade testing has the potential to identify other PGVs in addition to those detected in the probands. Clinical trial information: UMIN000046085 .

Celiac disease: Who should I test, and how?

First-degree relatives of patients with celiac disease and patients with dermatitis herpetiformis, type 1 diabetes mellitus, and autoimmune thyroid disease are among those for whom testing is advisable.

Risk of Syndrome-Associated Cancers Among First-Degree Relatives of Patients With Pancreatic Ductal Adenocarcinoma With Pathogenic or Likely Pathogenic Germline Variants

Increased cancer risk in first-degree relatives of probands with pancreatic ductal adenocarcinoma (PDAC probands) who carry pathogenic or likely pathogenic germline variants (PGVs) in cancer syndrome-associated genes encourages cascade genetic testing. To date, unbiased risk estimates for the development of cancers on a gene-specific basis have not been assessed. To quantify the risk of development of PDAC and extra-PDAC among first-degree relatives of PDAC probands who carry a PGV in 1 of 9 cancer syndrome-associated genes-ATM, BRCA1, BRCA2, PALB2, MLH1, MSH2, MSH6, PMS2, and CDKN2A. This case series focused on first-degree relatives of PDAC probands carrying PGVs in specific cancer syndrome-associated genes. The cohort comprised clinic-ascertained patients enrolled in the Mayo Clinic Biospecimen Resource for Pancreas Research registry with germline genetic testing. In total, 234 PDAC probands carrying PGVs were drawn from the prospective research registry of 4562 participants who had undergone genetic testing of cancer syndrome-associated genes. Demographic and cancer-related family histories were obtained by questionnaire. The data were collected from October 1, 2000, to December 31, 2021. For the PDAC probands, the genetic test results of the presence of PGVs in 9 cancer syndrome-associated genes were obtained by clinical testing. Cancers (ovary, breast, uterus or endometrial, colon, malignant melanoma, and pancreas) among first-degree relatives were reported by the probands. Standardized incidence ratios (SIRs) were used to estimate cancer risks among first-degree relatives of PDAC probands carrying a PGV. In total, 1670 first-degree relatives (mean [SD] age, 58.1 [17.8] years; 853 male [51.1%]) of 234 PDAC probands (mean [SD] age, 62.5 [10.1] years; 124 male [53.0%]; 219 [94.4%] White; 225 [98.7%] non-Hispanic or non-Latino]) were included in the study. There was a significantly increased risk of ovarian cancer in female first-degree relatives of probands who had variants in BRCA1 (SIR, 9.49; 95% CI, 3.06-22.14) and BRCA2 (SIR, 3.72; 95% CI, 1.36-8.11). Breast cancer risks were higher with BRCA2 variants (SIR, 2.62; 95% CI, 1.89-3.54). The risks of uterine or endometrial cancer (SIR, 6.53; 95% CI, 2.81-12.86) and colon cancer (SIR, 5.83; 95% CI, 3.70-8.75) were increased in first-degree relatives of probands who carried Lynch syndrome mismatch repair variants. Risk of PDAC was also increased for variants in ATM (SIR, 4.53; 95% CI, 2.69-7.16), BRCA2 (SIR, 3.45; 95% CI, 1.72-6.17), CDKN2A (SIR, 7.38; 95% CI, 3.18-14.54), and PALB2 (SIR, 5.39; 95% CI, 1.45-13.79). Melanoma risk was elevated for first-degree relatives of probands with CDKN2A variants (SIR, 7.47; 95% CI, 3.97-12.77). In this case series, the presence of PGVs in 9 cancer syndrome-associated genes in PDAC probands was found to be associated with increased risk of 6 types of cancers in first-degree relatives. These gene-specific PDAC and extra-PDAC cancer risks may provide justification for clinicians to counsel first-degree relatives about the relevance and importance of genetic cascade testing, with the goal of higher uptake of testing.

Prevalence of Traditional Risk Factors in First-Degree Relatives of Patients With Established Cardiovascular Disease.

World Health Organization (WHO)/International Society of Hypertension (ISH) risk prediction charts are useful for predicting 10-year combined myocardial infarction and stroke risk (fatal and non-fatal). Hence the current study was conducted to assess the 10-year risk of cardiovascular disease among adults in Ahmedabad, India. The primary aim of the study was to assess the cardiovascular risk among first-degree relatives of patients attending the outpatient clinic. Also, to create awareness regarding assessment of cardiovascular risk among the studied group. A cross-sectional study was carried out among 372 first-degree relatives of patients at an out-patient cardiology clinic present in Vadaj, Ahmedabad. The WHO/ISH risk prediction chart for South-East Asia Region D (SEAR D) was used for calculating the 10-year cardiovascular risk. A maximum (80.10%) of the study participants were in the low-risk (<10%) category followed by 8.33% for moderate-risk (10-20%), 7.25% for moderately high-risk (20-30%), 2.42% for high-risk (30-40%) and 1.88% for very high-risk (>40%). WHO/ISH risk prediction charts provide a quick and effective way to assess and categorize the population in a low-resource setting which in turn helps in delivering focused intervention to the high-risk groups.

Familial Co-Aggregation of Idiopathic Inflammatory Myopathies and Cancer: A Swedish Population-Based Study.

To examine if idiopathic inflammatory myopathies (IIMs) share familial susceptibility with cancer, we estimated the familial co-aggregation of these diseases. This Swedish population-based family study with data from national registers included 8,460 first-degree relatives of patients with IIM and 41,127 relatives of matched individuals without IIM. We modeled the adjusted odds ratios (ORs) of familial co-aggregation of IIM and cancer using conditional logistic regressions and adjusted for sex and birth year of index individuals and their first-degree relatives. We examined the associations for cancer overall and stratified by several factors of interest. We also performed exploratory analyses for specific cancer types. We observed no statistically significant familial associations between IIM and cancer overall. However, there was a familial association in male relative pairs of patients with dermatomyositis (adjusted OR for familial association 1.39 [95% confidence interval (95% CI) 1.15-1.68]). The association remained statistically significant after controlling for multiple testing. Moreover, this finding was consistent between kinships. Familial co-aggregation of IIM and cancer diagnosed before 50 years of age was only observed in offspring. In exploratory analyses, only the familial associations for myeloid malignancies (adjusted OR 2.27 [95% CI 1.43-3.60]) and liver cancer (adjusted OR 2.01 [95% CI 1.21-3.33]) in male relative pairs remained significant after controlling for multiple testing. We found little evidence of shared familial susceptibility as a major pathologic mechanism contributing to the co-occurrence of IIM and cancer overall. There could be subsets of patients and cancer types for which familial factors including genetics and shared environments are of more importance, but these findings need replication.

Prevalence of Prediabetes in First Degree Relatives of Patients with Type 2 Diabetes Mellitus in a Tertiary Centre in Southern Nigeria

<i>Introduction:</i> Prediabetes confers about a sixfold increased risk of diabetes and a two to threefold increased risk of cardiovascular events. A family history of diabetes is a major risk factor for the development of diabetes. The detection of prediabetes in its early stages in persons at risk could lead to the delay or prevention of the disease and subsequent adverse sequalae. <i>Methods:</i> A total of 180 first-degree relatives (FDR) of patients with type 2 diabetes and 90 controls were assessed. A fasting venous blood sample was collected for fasting plasma glucose. Following 75g of anhydrous glucose ingestion, the 2-hour post glucose load and glycated haemoglobin was assessed. Statistical significance was set at a p value <0.05. <i>Results:</i> The mean age of the cases who were first degree relatives of type 2 DM was 38.2±12.3 years with a female to male ratio of 1.4:1. The prevalence of prediabetes was 23.9% which was significantly higher than in the controls (10%; χ²=8.385, p=0.015). Using the various indices of glycaemic control, impaired fasting glucose, impaired glucose tolerance and elevated HbA1c in the FDR’s was found in 15.0%, 12.2% and 15.6% respectively. <i>Conclusion:</i> Relatives of Type 2 DM patients should be considered as primary target for diabetes preventive programs as this will necessitate institution of effective measures early to delay or prevent the onset of type 2 diabetes mellitus.

Genetic variants and risk of endocrine autoimmunity in relatives of patients with Addison's disease.

Since individuals with Addison's disease (AD) present considerable co-occurrence of additional autoimmune conditions, clustering of autoimmunity was also predicted among their relatives. The study was aimed to assess circulating autoantibodies in first-degree relatives of patients with AD and to correlate them with the established genetic risk factors (PTPN22 rs2476601, CTLA4 rs231775, and BACH2 rs3757247). Antibodies were evaluated using validated commercial assays, and genotyping was performed using TaqMan chemistry. The studied cohort comprised 112 female and 75 male relatives. Circulating autoantibodies were found in 69 relatives (36.9%). Thyroid autoantibodies, that is antibodies to thyroid peroxidase (aTPO) and thyroglobulin (aTg), were detectable in 25.1 and 17.1% relatives, respectively. Antibodies to 21-hydroxylase (a21OH) were found in 5.8% individuals, and beta cell-specific antibodies to ZnT8, GAD, and IA2 were found in 7.5, 8.0, and 2.7%, respectively. The prevalence of a21OH (P = 0.0075; odds ratio (OR) 7.68; 95% CI 1.903-36.0), aTPO (P < 0.0001; OR 3.85; 95% CI 1.873-7.495), and aTg (P < 0.0001; OR 7.73; 95% CI 3.112-19.65), as well as aGAD (P = 0.0303; OR 3.38; 95% CI 1.180-9.123) and aZnT8 (P = 0.032; OR 6.40; 95% CI 1.846-21.91), was significantly increased in carriers of rs2476601 T allele. Moreover, T allele appeared to be a risk factor for multiple circulating autoantibody specificities (P = 0.0009; OR 5.79; 95% CI 1.962-15.81). None of the studied autoantibodies demonstrated significant association with rs231775 in CTLA4 (P > 0.05), and only weak association was detected between BACH2 rs3757247 and circulating aTPO (P = 0.0336; OR 2.12; 95%CI 1.019-4.228). In conclusion, first-degree relatives of patients with AD, carriers of the PTPN22 rs2476601 T allele, are at particular risk of developing autoantibodies to endocrine antigens.

Predictive factors based on the health belief model on cancer screening behaviour in first degree relatives of patients with Lynch syndrome-associated colorectal cancer

ObjectivesThis study aimed to investigate colorectal cancer-related knowledge, health beliefs, and screening behaviour in first-degree relatives (FDRs) of patients with Lynch syndrome-associated colorectal cancer (CRC) and explore the predictive factors of screening behaviour based on a health belief model. MethodsThis cross-sectional study was conducted in the colorectal department of a Class A tertiary hospital in Guangzhou from December 2017 to December 2019. A total of 265 FDRs of 96 patients with Lynch syndrome-related CRC were selected. The study was conducted in the colorectal department of a tertiary cancer centre in Guangzhou. The demographic questionnaire, the simplified CRC knowledge questionnaire, and the Champion’s Health Belief Model Scale were used for evaluation. Data were analyzed using statistical description, between-group comparisons, and binary logistic regression. ResultsA total of 160 (60.4%), 61 (23.0%), and 44 (16.6%) of the participants had high, medium, and low levels of knowledge about CRC, respectively; the average overall score of health belief was 121.36 ± 13.02. Sixty-one participants (23.0%) underwent Lynch syndrome-associated cancer screening. The predictive factors of screening behaviour included sex (male), age (older), married status (married), multiple primary cancers of the index patients, and high levels of knowledge and health beliefs (P < 0.05). ConclusionsThe knowledge and health beliefs of cancer and cancer screening in FDRs of patients with Lynch syndrome-associated CRC should be improved. Both knowledge and beliefs are critical in promoting their cancer screening behaviour. Interventions should focus on health education and enhance health beliefs of the FDRs for better screening behaviour.

Risk Prediction of New Intracranial Aneurysms at Follow-Up Screening in People With a Positive Family History.

In first-degree relatives of patients with aneurysmal subarachnoid hemorrhage (aSAH), the risk of an intracranial aneurysm can be predicted at initial screening but not at follow-up screening. We aimed to develop a model for predicting the probability of a new intracranial aneurysm after initial screening in people with a positive family history of aSAH. In a prospective study, we obtained data from follow-up screening for aneurysms of 499 subjects with ≥2 affected first-degree relatives. Screening took place at the University Medical Center Utrecht, the Netherlands, and the University Hospital of Nantes, France. We studied associations between potential predictors and the presence of aneurysms using Cox regression analysis and the predictive performance at 5, 10, and 15 years after initial screening using C statistics and calibration plots, while correcting for overfitting. In 5050 person-years of follow-up, intracranial aneurysms were found in 52 subjects. The risk of aneurysm at 5 years was 2% to 12%, at 10 years, 4% to 28%, and at 15 years, 7% to 40%. Predictors were female sex, history of intracranial aneurysms/aneurysmal subarachnoid hemorrhage, and older age. The sex, previous history of intracranial aneurysm/aSAH, older age score had a C statistic of 0.70 (95% CI, 0.61-0.78) at 5 years, 0.71 (95% CI, 0.64-0.78) at 10 years, and 0.70 (95% CI, 0.63-0.76) at 15 years and showed good calibration. The sex, previous history of intracranial aneurysm/aSAH, older age score provides risk estimates for finding new intracranial aneurysms at 5, 10, and 15 years after initial screening, based on 3 easily retrievable predictors; this can help to define a personalized screening strategy after initial screening in people with a positive family history for aSAH.

Radiographic Lung Abnormalities in First-Degree Relatives of Patients With Different Subtypes of Pulmonary Fibrosis

Early interstitial lung disease (ILD) has been detected in 14% to 22% of screened relatives of patients with familial pulmonary fibrosis.1,2 Relatives of patients with sporadic IPF have been found with a higher prevalence of interstitial lung abnormalities (ILA) and preclinical ILD than the general population.3 Despite advances made in screening, many previous cohorts have excluded individuals with nonidiopathic pulmonary fibrosis (IPF) ILD. Therefore, we sought to determine the prevalence of subclinical ILD in family members of patients with fibrotic ILD, regardless of subtype.