Disease In Family Members Research Articles

Complex Story of the Genetic Origins of Pediatric Heart Disease

Pediatric heart disease, aka cardiovascular disease in the young, comprises varied phenotypes, including cardiovascular malformations, cardiomyopathies, vasculopathies (eg, Marfan syndrome), and cardiac arrhythmias. Cardiovascular malformations are a major component of pediatric heart disease and constitute a substantial portion of clinically significant birth defects, with a definition-dependent estimated incidence of 4 to 50 per 1000 live births.1,2 Despite advances in diagnosis and therapy, the morbidity and mortality associated with cardiovascular malformations and other forms of pediatric heart disease make them important clinical problems. Thus, there has been considerable interest in understanding their cause. Article see p 1313 Because of early recognition of environmental teratogens such as rubella, thalidomide, and high altitude, considerable attention was focused on environmental factors; however, in the Baltimore-Washington Infant Study,3 common risk factors identified for pediatric heart disease were positive family history and maternal diabetes mellitus. Numerous examples of increased risk of pediatric heart disease in family members of affected individuals have been published.4 The association of cardiovascular malformations and other birth defects with chromosomal abnormalities5 provides further support for a genetic origin. Based on studies of recurrence and transmission risks, a hypothesis of multifactorial origin was proposed.6 In this type of inheritance, an individual’s genetic predisposition interacts with other genes and/or environmental factors to cause heart disease. However, in the past 2 decades, mendelian inheritance models have been used to exploit molecular genetic and cytogenetic observations in multiplex families.7 The discovery that heterozygous mutation of the transcription factor NKX2.5 causes …

Analysis of serum levels of IgA antibodies to Epstein Barr virus capsid antigens in the spouses and the children of patients with nasopharyngeal carcinoma

Objective To analyze the serum levels of IgA antibodies to Epstein Barr virus capsid antigens (EBV/IgA/VCA) in patients with nasopharyngeal carcinoma (NPC) and in their spouses and children in order to further evaluate the risk of developing the disease in family members of NPC patients.

“Non-white”: a candidate for the lexical room 101

<h3>Background</h3> A positive family history (PFH) of spondyloarthritis (SpA) is considered a risk indicator for the presence of axial spondyloarthritis (axSpA) in patients with chronic back pain (CBP). In the...

Pleural plaques related to &amp;quot;take-home&amp;quot; exposure to asbestos: An international case series

While a large number of studies indicate the risks of high-level exposures to asbestos in the workplace setting, a relatively small number of studies describe the risk of pleural disease related to "take-home" asbestos brought into the household by workers exposed to asbestos. Consequently, the risk of pleural disease in family members of asbestos-exposed workers is likely underappreciated. Two families of siblings, one in Israel and one in the US, were evaluated because of their significant exposures to asbestos brought into the home by family members with heavy occupational exposures. Two of the four children of an asbestos cement debagger in Petach Tikvah, Israel and two children of a pipe lagger in a naval shipyard near Seattle, Washington, manifested benign pleural disease without parenchymal disease, despite having no occupational exposure to asbestos. These cases illustrate that "take-home" asbestos exposure may lead to pleural disease at higher rates than commonly realized. Providers should recognize that due to the potential for "take-home" exposures, asbestos-related disease in a patient may be a marker for disease in household contacts. Patients with family members heavily exposed to asbestos should be strongly encouraged to quit smoking in an effort to reduce any further carcinogenic exposures. Additionally, workplace control and regulation of asbestos use should be emphasized to protect both workers and their families.

Reduced proportions of natural killer T cells are present in the relatives of lupus patients and are associated with autoimmunity

IntroductionSystemic lupus erythematosus is a genetically complex disease. Currently, the precise allelic polymorphisms associated with this condition remain largely unidentified. In part this reflects the fact that multiple genes, each having a relatively minor effect, act in concert to produce disease. Given this complexity, analysis of subclinical phenotypes may aid in the identification of susceptibility alleles. Here, we used flow cytometry to investigate whether some of the immune abnormalities that are seen in the peripheral blood lymphocyte population of lupus patients are seen in their first-degree relatives.MethodsPeripheral blood mononuclear cells were isolated from the subjects, stained with fluorochrome-conjugated monoclonal antibodies to identify various cellular subsets, and analyzed by flow cytometry.ResultsWe found reduced proportions of natural killer (NK)T cells among 367 first-degree relatives of lupus patients as compared with 102 control individuals. There were also slightly increased proportions of memory B and T cells, suggesting increased chronic low-grade activation of the immune system in first-degree relatives. However, only the deficiency of NKT cells was associated with a positive anti-nuclear antibody test and clinical autoimmune disease in family members. There was a significant association between mean parental, sibling, and proband values for the proportion of NKT cells, suggesting that this is a heritable trait.ConclusionsThe findings suggest that analysis of cellular phenotypes may enhance the ability to detect subclinical lupus and that genetically determined altered immunoregulation by NKT cells predisposes first-degree relatives of lupus patients to the development of autoimmunity.

When Do Family Members Have a Right to Know Genetic Information About a Patient?

Source: Gilbar R. Communicating genetic information in the family: the familial relationship as the forgotten factor. J Med Ethics. 2007;337:390–393; doi:10.1136/jme.2006.017467Because genetic information about a patient may have implications for other family members, physicians or genetic counselors may find themselves struggling between the duty to respect patient confidentiality and the felt obligation to disclose important information to a family member of a patient. Whether family members have a right to this information is a source of vigorous debate. A patient may have an interest in maintaining the confidentiality of his or her genetic inheritance, even from family members. The usual perception of the patient and various relatives as separate parties may result in a doctor-patient relationship which focuses only on the patient’s wishes while excluding any consideration of interests other members of the family might have in that genetic information. This article from the School of Law, Netanya Academic College, Tel-Aviv, Israel, suggests an alternative, more familial understanding of medical confidentiality with regard to genetic information.The disclosure of genetic information without the consent of the patient is usually justified only to prevent serious harm or death to others. Conflicts are resolved by giving the doctor and patient discretion to decide whether to inform family members. Criteria used in considering disclosure include: the availability of treatment for the genetic condition; the availability of the genetic test and its accuracy in assessing risk; the likelihood of disease in family members; the severity of disease and the nature of the disease; and the likelihood of strong emotional reactions when family members are provided with the information. The author proposes we add consideration of the effect any decision will have on the relationships and dynamics of the particular family, thus relaxing confidentiality to “provide room for the ethics of the family, which is mainly based on care, commitment, intimacy, solidarity and mutual responsibility.” Such an addition will require deliberations between doctor and patient and within the family to determine who and when to tell, and how much will be told to each individual. The author hypothesizes that as research develops in the area of genetics, the family, rather than the individual, will be seen as the unit of care.Dr. Ross has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.Gilbar proposes that health care practitioners who communicate genetic information to individual patients must be prepared to engage the family in the decision-making process regarding the disclosure of genetic information. He argues for considering both the expected emotional reactions of individual family members and the effect disclosure or non-disclosure may have on familial relationships and family dynamics. To do this, he acknowledges that a physician will need “close knowledge of the nature of the patient’s familial relationship.” He seeks communication and deliberation both between the doctor and patient and within the family. He argues that this “deliberative approach” requires a “relaxation of medical confidentiality and privacy.”While the deliberative approach is most often used in medicine to refer to public discourse regarding health policy,1–3 Gil-bar notes that others4 have used it in the context of ethics and communication in health care decision-making about genetic information. This approach focuses less on the actual outcome and more on creating a decision-making process that allows for growth of moral development and moral agency.4Even if one were to agree with Gilbar that 1) patients should acknowledge the interests of family members in decision-making, and 2) it is optimal when patients can explore the familial implications of genetic tests with their biological families, it is not clear that Gilbar’s conclusion to relax confidentiality based on deliberative methodology is valid. While this approach may help patients accept that it may be best to share information and to involve family members, physicians do not necessarily have the moral authority to demand that patients share information within their family or that patients must always involve their families.4 Even after deliberation, there may be cases in which it is appropriate for decisions “to be the concern of individual patients alone irrespective of the wishes and interests of their families.”4 While the health care practitioner should offer to mediate and to provide a safe environment for familial discussions to take place, in some cases patients may demand strict confidentiality. The relaxation of medical confidentiality can be encouraged, but not enforced!When trying to find a path through deep weeds it is best to have a partner. Faced with a felt need to disclose a patient’s genetic information and a sense that such disclosure will be problematic, the prudent clinician will consult early in the process with a knowledgeable third party – such as a Hospital Ethics Committee – before getting lost in this ethical swamp.

Screening for Celiac Disease in Family Members: Is Follow-up Testing Necessary?

Celiac disease is a genetically determined intolerance to gluten that results in villous atrophy in the small intestine. Because celiac disease occurs in families, relatives of affected individuals are tested for the disease. However, there are no evidence-based guidelines for when, or how often, to test relatives. Our goal was to determine if one-time screening of relatives is sufficient. Of 171 family members with an initially negative endomysial antibody who were tested on more than one occasion, 6 (3.5%) were positive on repeat testing. The average time to seroconversion was 1.7+/-1.2 years (range, 6 months-3 years 2 months). Only one of the seroconverters had diarrhea; the remainder were asymptomatic. None of the patients had a change in symptoms between testing. We conclude that one-time testing for celiac disease among families with affected members is insufficient. Repeat testing should occur irrespective of the presence of symptoms.

Immunofluorescence detection of globotriaosylceramide deposits in conjunctival biopsies of Fabry disease patients

Fabry disease is an X-linked disorder due to a deficiency of alpha-galactosidase A and leads to the accumulation of globotriaosylceramide (Gb3) in various cells. The detection of Gb3 deposits may help in the diagnosis. To date, no immunofluorescence-specific detection of Gb3 in conjunctival biopsies has been reported. The aim of this work was to detect Gb3 accumulation in conjunctival biopsies from Fabry patients by immunofluorescence. Conjunctival biopsies taken from Fabry males and females, before and after enzyme replacement therapy, and normal controls were processed for immunofluorescence with a monoclonal antibody specific for Gb3. Positive green immunofluorescence was observed in all biopsies from Fabry patients before enzyme replacement therapy. After 6 months of treatment, immunofluorescence in blood vessels was not observed. Immunofluorescence detection of Gb3 in conjunctival biopsies may be a reliable method for the diagnosis of Fabry disease in family members, and to evaluate effectiveness of enzyme replacement therapy.

Celiac Disease Genetics: Current Concepts and Practical Applications

Celiac disease is a multifactorial disease with complex genetics. Both HLA and non-HLA genes contribute to the genetic component, but recent findings suggest that the importance of non-HLA genes might have been overestimated. No susceptibility genes other than HLA-DQ have yet been identified in celiac disease. In contrast to the meager knowledge regarding non-HLA genes, we have acquired a detailed understanding about which HLA genes are predisposing for disease, and how they are involved in the pathogenesis. This knowledge might pave the road for novel treatments for the disease. The role of HLA as a necessary, but not sufficient, genetic factor can moreover be used for diagnostic purposes to exclude a celiac disease diagnosis. The applicability of HLA genotyping is particularly useful for excluding celiac disease in family members or risk groups with fairly unbiased distribution of HLA alleles (ie, patients with Turner syndrome and patients with Down syndrome) and in patients with a clinical suspicion of celiac disease.

Privacy and medical research

Privacy and medical research

A fourfold difference in the incidence of type 1 diabetes between Sweden and Lithuania but similar prevalence of autoimmunity

We investigated whether other autoimmune disorders in addition to type 1 diabetes are more common in Sweden than Lithuania, and if there are any differences in inheritance patterns of both type 1 diabetes and other autoimmune disorders. Data from 517 children in southeast Sweden and 286 children in Lithuania aged 0–15 years were included in the study. Age- and sex-matched control children were randomly selected. Information was collected by questionnaire. Of the children with diabetes in Sweden, 13.2% had a family member with type 1 diabetes compared to 7% of children with diabetes in Lithuania ( P<0.01) (OR=2.01). No such difference was seen for other autoimmune diseases in family members of children with diabetes (Sweden 12%, Lithuania 14%, n.s.). Control children in Lithuania had family members with autoimmunity more frequently (15.3%) than control children in Sweden (7.4%, P<0.001) (OR=2.26). This difference was most pronounced in mothers. The Lithuanian control children had an autoimmune disease more frequently than the controls in Sweden (4.7% versus 1.5%, respectively, P<0.001) (OR=3.21). There seem to be environmental factors that specifically contribute to the development of type 1 diabetes, factors which are less related to the development of autoimmunity in general.

A fourfold difference in the incidence of type 1 diabetes between Sweden and Lithuania but similar prevalence of autoimmunity

<h2>Abstract</h2> We investigated whether other autoimmune disorders in addition to type 1 diabetes are more common in Sweden than Lithuania, and if there are any differences in inheritance patterns of both type 1 diabetes and other autoimmune disorders. Data from 517 children in southeast Sweden and 286 children in Lithuania aged 0–15 years were included in the study. Age- and sex-matched control children were randomly selected. Information was collected by questionnaire. Of the children with diabetes in Sweden, 13.2% had a family member with type 1 diabetes compared to 7% of children with diabetes in Lithuania (<i>P</i><0.01) (OR=2.01). No such difference was seen for other autoimmune diseases in family members of children with diabetes (Sweden 12%, Lithuania 14%, n.s.). Control children in Lithuania had family members with autoimmunity more frequently (15.3%) than control children in Sweden (7.4%, <i>P</i><0.001) (OR=2.26). This difference was most pronounced in mothers. The Lithuanian control children had an autoimmune disease more frequently than the controls in Sweden (4.7% versus 1.5%, respectively, <i>P</i><0.001) (OR=3.21). There seem to be environmental factors that specifically contribute to the development of type 1 diabetes, factors which are less related to the development of autoimmunity in general.

Familial Primary Biliary Cirrhosis in Hiroshima

Primary biliary cirrhosis (PBC) is an autoimmune liver disease characterized by the presence of anti-mitochondrial antibodies and chronic inflammatory destruction of septal and intrahepatic bile ducts. Although there are no obvious associations of PBC with MHC class I or class II genes, there appears to be a significant increased risk of developing disease within families. Clearly, a combination of genetic and environmental factors play a role in disease pathogenesis, although the relative contributions of each are unclear. In this study, we have taken advantage of the well-defined health-care system in Hiroshima prefecture, where PBC is a reportable disease. In the period 1988–1997, 156 new patients with PBC in a total population of 2,873,000 were diagnosed. These patients included 18 subjects that were derived from eight different families in which more than one family member had a history of PBC; this reflects a frequency of 5.1% and further shows that the prevalence of PBC is greatly increased in family members. Of interest, the median age of onset of PBC in second generation patients was much younger (33.4±10.8 years) compared to median disease onset in general patients with PBC in Hiroshima (55.6±12 years). In fact, it was striking that the onset of disease in family members often occurred within a few years of each other. We also noted that sera of affected members had similar AMA reactive profiles against recombinant PDC-E2, BCKD-E2 and OGDC-E2; the major autoantigens of PBC. Similar HLA types were found within affected members of a pedigree but the data is limited because of absence of similar typing of unaffected members. The increased family history of PBC, and the earlier onset of disease in second generation members, suggests that environmental agents are an important risk factor for the development of disease. We suggest that genomic analysis in familial PBC will be important to identify the mechanisms of genetic susceptibility.

Sera from Children with Type 1 Diabetes mellitus React against a New Group of Antigens Composed of Lysophospholipids

Several autoantibodies related to Type 1 diabetes mellitus and their corresponding autoantigens have been previously identified. While peptide antigens are more widely recognized, lipid antigens like sulfatides and gangliosides are also known epitopes for the diabetic humoral immune response. Islet cell antibodies (ICA) in Type 1 diabetes are heterogeneous immunoglobulins directed against selected antigens in the islets of Langerhans. Moreover, ICA may be the best predictive marker of disease in family members of patients with Type 1 diabetes. The aims of this study were: (1) to purify lipids from porcine pancreas that contain ICA epitopes; (2) to characterize these lipid antigens, and (3) to use the purified lipids in an assay to detect antibodies in patients with Type 1 diabetes. A unique family of 4 lysophospholipids, 1 fully characterized as lysophosphatidylmyoinositol, partially inhibited ICA staining, and therefore, were considered to be candidate antigens for an ICA immunoassay. Using a dot blot immunoassay, we detected antibodies directed against these phospholipids in 28 out of 46 (61%) diabetic sera, while detecting only 1 false positive out of 28 nondiabetic sera (3.6%; p < 0.0001 comparing diabetic vs. nondiabetic serum). Therefore, lysophospholipid immunoassay positivity is present in sera of Type 1 diabetic patients. Furthermore, we detected 15 out of 23 ICA-negative diabetic sera (65.2%), showing that our phospholipid immunoassay does not correlate with ICA positivity.

Characterization of obstructive airway disease in family members of probands with asthma. An algorithm for the diagnosis of asthma.

To investigate the genetic susceptibility to asthma, we developed an algorithm to classify the phenotype of each family member enrolled in a family study on the genetics of asthma. This algorithm was applied to 92, two- and three-generation families, identified through a subject (proband) with asthma first diagnosed 25 yr previously. The algorithm consisted of five classes based on the presence or absence of bronchial hyperresponsiveness (BHR), respiratory symptoms, smoking, airways obstruction, and bronchodilator reversibility. All family members were classified as: (1) definite asthma; (2) probable asthma; (3) unclassifiable airway disease; (4) chronic obstructive pulmonary disease (COPD); (5) unaffected (without clinical evidence of asthma and COPD). Thirteen of the 92 probands (14%) could not be classified as asthmatic when retested 25 yr later because of loss of BHR, loss of bronchodilator reversibility, or a current history of cigarette smoking. Of the 265 first-degree offspring, 49 (18%) were classified as having definite asthma (Class 1), and 22 (8%) as probable asthma (Class 2). A large number of offspring with clinical evidence of asthma did not have a prior physician's diagnosis of asthma, and offspring in Class 1 (definite asthma), with and without a physician's diagnosis, had similar clinical and physiologic characteristics. These results support the usefulness of this approach to classify subjects with asthma for genetic epidemiologic studies and show that reliance on a prior physician's diagnosis may result in misclassification or underdiagnosis. Characterization of the offspring in this family study showed that there is familial clustering, which supports the presence of a hereditary component in asthma.

Relationship between site of disease and familial occurrence in Crohn's disease.

Concordance in the extent of disease among the family members of patients with Crohn's disease has not been widely investigated. Furthermore, the relationship between the site of the disease and familial occurrence has never been studied. Our aim was to evaluate the familial occurrence of Crohn's disease in the various sites. Nine hundred thirty-four patients with Crohn's disease, observed consecutively in two gastrointestinal departments, were investigated to determine first-degree familial incidence (in both Crohn's disease and ulcerative colitis). Whenever two or more members were attending the same clinic, only one was regarded as a propositus. The analysis, therefore, was carried out on 882 patients. The exact site of the disease was determined in all patients either at diagnosis or during the follow-up by colonoscopy and by small bowel enema. The rate of concordance in the extent of disease and familial occurrence in the various sites was evaluated and the difference was calculated by chi-square test. Sixty-one propositi were identified among all the patients. Forty-nine had familial occurrence for the same disease (concordant patients), whereas 12 had at least one relative with ulcerative colitis (discordant patients). In 44 propositi with only one relative affected, the rates of concordance in the extent of the disease were 84, 68, 18, and 0% respectively, for the ileum, the ileum-right colon, the ileum-total colon, and the colon. The number of propositi in the various sites was as follows: 4 of 162 (2.4%) patients with the disease located in the colon, 1 of 9 (11%) with the jejunum site, 24 of 380 (6.3%) with the ileum site, 16 of 165 (9.7%) with the ileum and right colon site, and 16 of 164 (9.7%) with the ileum and total colon site. The chi-square values of propositi distribution among other sites and the colon was, respectively, as follows: jejunum, 2.2 (N.S.); ileum, 3.4 (P = 0.06); ileum and right colon, 7.4 (P = 0.006); and ileum and total colon, 7.4 (P = 0.006). This study shows a pronounced concordance in the site of the disease for family members with Crohn's disease and suggests that familial occurrence in Crohn's disease is less frequent when the disease is located in the colon rather than elsewhere.

Prevalence of autoimmune diseases in the family members of patients with pemphigus vulgaris.

Several studies show that the family members of patients with autoimmune diseases are more susceptible to the development of the same or, more frequently, other autoimmune diseases. Although an association between pemphigus vulgaris (PV) and other autoimmune diseases has been reported, the presence of autoimmune diseases in the family members of patients with PV has not been studied. The purpose of this study was to determine whether first-degree relatives of patients with PV are more susceptible to the development of autoimmune diseases. A case-control study was done. A total of 830 first-degree relatives of 60 white patients with PV were compared with 890 relatives of 60 age-, race-, and sex-matched random controls. Both groups of relatives were screened for the presence of 16 autoimmune diseases. There was a highly significant increase in the prevalence of autoimmune diseases in the first-degree family members of PV patients, compared with controls. There is an increased susceptibility to the development of autoimmune diseases in the family members of patients with PV.

Occupational and environmental exposure to lead and Paget's disease of bone

This paper reports an association between lead exposure and Paget's disease of bone. Detailed interviews of occupational or environmental exposure to lead established this association in 44 of 48 male patients, i.e., in 92% of the total number of patients or in all patients who were interviewed. Life-long occupational and environmental histories were also obtained from two other categories of patients with Paget's disease: from a small number of females with this disease and from affected relatives of patients with Paget's disease. Paget's disease in family members has been reported by others to be linked to genetic factors. The histories of the small number of these two categories of patients with Paget's disease; the females and the family members, revealed occupational or environmental exposure to a toxic substance, primarily to lead, in the past. This presentation also hypothesizes that lead-exposure is the basis for hyperparathyroidism, which coexists in patients with Paget's disease of bone. It also deals with the attempted correlation of lead contamination in different areas and the prevalence of Paget's disease.

X-Linked hypophosphatemic rickets: a disease often unknown to affected patients

X-Linked hypophosphatemic rickets (XLH) is an X-linked dominant disorder that is secondary to renal phosphate wasting. Affected individuals frequently present the following characteristics: short stature, lower-extremity deformity, bone pain, dental abscesses, en-thesopathy, rickets, and osteomalacia. Since the disorder is characterized by evident phenotypic abnormalities, we hypothesized that there would be a high degree of knowledge about the disease in affected kindreds. Thus, we constructed a six-page, self-administered questionnaire to determine whether family members are, in fact, aware of their disease and properly diagnosed and treated. We also designed the survey to determine rates of symptoms thought to be associated with rickets/osteomalacia in a population with a lower referral bias than is usually seen in tertiary care centers. We administered the questionnaire to 234 study subjects (57 affected) who were members of one of three large kindreds. Although 62% of affected individuals knew they had some problem with their bones, only 22.6% were told by a physician that they had rickets or osteomalacia. This apparent lack of awareness occurred in spite of 61.1% of affected subjects complaining of bone or joint problems to their personal physician. Indeed, of those patients who had persistent complaints, only 34.5% were told they had rickets or osteomalacia. Only one patient was taking phosphate and vitamin D. The spectrum of symptoms evident in affected subjects compared with normals included: dental abscesses (54.5% vs. 13.0%, P < 0.001), bone pain (45.5% vs. 28.2%, P = 0.027), back pain (51.8% vs. 35.1%, P = 0.036), joint stiffness (48.2% vs. 16.8%, P < 0.001), joint pain (55.4% vs. 31.1%, P = 0.003), weakness (25.0% vs. 10.7%, P = 0.023), and hearing loss (28.6% vs. 9.8%, P = 0.002). Surprisingly, although affected individuals complained of many symptoms due to XLH, they fractured bones less frequently than controls (20% vs. 38.1%., P = 0.018). Our data demonstrate that, despite the presence of disease in family members, few affected subjects knew that they had XLH. Although the presence of symptoms did increase knowledge of disease status, only one-third of symptomatic individuals knew of their diagnosis.

Intrafamilial transmission of hepatitis C virus: The important role of inapparent transmission

To evaluate the intrafamilial transmission of hepatitis C virus (HCV) 104 index patients with type C chronic liver disease and their 307 family contacts were interviewed. After a questionnaire on the risk factors of parenteral exposure, blood samples were obtained and tested for liver biochemistry and anti-HCV antibody by enzyme-linked immunosorbent assay (Abbott II). Overall, 52 family contacts (17%) were positive for anti-HCV, indicating a higher anti-HCV prevalence among family contacts than among the general population in Taiwan. The anti-HCV prevalences in parents, spouses, children, and other contacts of the patients were 54% (14/26), 28% (25/91), 6.9% (10/143), and 6.4% (3/47), respectively. The contacts of index patients had increasingly greater risk of HCV infection when they became older and had lived longer with index patients. All family contacts were divided into two groups categorized by whether the index patients had or did not have a history of parenteral exposure. Among 126 family contacts of the 42 patients without parenteral exposure, blood transfusion and surgery were the factors significantly associated with HCV infection in these family contacts (odds ratio = 7.26, 95% confidence interval = 2.32-32.67; odds ratio = 3.95, 95% CI = 1.29-12.11, respectively). Risk factors were not significantly associated with HCV infection among 181 family contacts of the 62 index patients with parenteral exposure. It is concluded that the index patients without parenteral exposure appeared to have acquired the disease from HCV-infected family members with risk factors. Most of the index patients had a history of parenteral exposure and in turn served as the source of the disease for family members.