Screen for MAOA mutations in target human groups.

Brunner et al. [1993: Am J Hum Genet 52: 1032-1039; 1993: Science 262:578-580] described males with an MAO-A deficiency state resulting from a premature stop codon in the coding region of the MAOA gene. This deficiency state was associated with abnormal levels of amines and amine metabolites in urine and plasma of affected males, as well as low normal intelligence and apparent difficulty in impulse control, including inappropriate sexual behavior. In the present study, disruption of the MAOA gene was evaluated in males with mental retardation with and without a history of sexually deviant behavior, as well as normal controls, healthy males, and patients with other diseases (Parkinson disease, Lesch-Nyhan syndrome). When available, plasma samples were evaluated first for levels of 3-methoxy, 4-hydroxyphenolglycol (MHPG), a metabolite of norepinephrine which serves as the most sensitive index of MAO-A activity in humans. Blood DNA from individuals with abnormally low MHPG, and from other individuals for whom metabolite levels were not available, were screened for nucleotide variations in the coding region of the MAOA gene by single-strand conformational polymorphism (SSCP) analysis across all 15 exons and splice junctions, and by sequencing, when indicated by either altered metabolites or SSCP shifts. No evidence for mutations disrupting the MAOA gene was found in 398 samples from the target populations, including institutionalized mentally retarded males (N = 352) and males participating in a sexual disorders clinic (N = 46), as well as control groups (N = 75). These studies indicate that MAOA deficiency states are not common in humans.

Intrafamilial transmission of hepatitis C virus.

Family members of hepatitis C virus (HCV)-infected hemodialysis patients had a high rate (8.1%) of HCV infection and were often infected by the same genotype of HCV as the renal patients. Renal patients who had a longer history of hemodialysis or more frequent arteriovenous shunt replacement posed a higher risk to their household contacts, especially to their primary-care providers at home.

A family cluster of an immune escape variant of hepatitis B virus infecting a mother and her two fully immunized children.

A hepatitis B virus (HBV) immune escape variant which results from a substitution of glycine by arginine at position 145 (arginine-145) in the immunodominant neutralization epitope of the S protein was found to infect one child in a seroepidemiologic survey of 1,812 vaccinated children. The child's mother and a younger brother were also infected by the same HBV variant, despite a greater than accepted level of protective antibody (anti-HBV surface antigen) in both the index child (30 mIU/ml) and the brother (> 20,000 mIU/ml). Our findings suggest the perinatal or horizontal transmission of the arginine-145 HBV variant from mother to child, but the ability of this variant to propagate among the vaccinated children remains unknown.

Altered antigenicity of 'a' determinant variants of hepatitis B virus.

The 'a' determinant of hepatitis B virus (HBV) surface antigen (HBsAg) is the most important target for diagnosis and immunoprophylaxis. Several HBV variants with point mutations within the 'a' determinant have been identified among fully vaccinated children in Taiwan. We investigated the effect of each of these mutations on the antigenic nature of the S protein by cloning and expression of the mutant S antigens in Pichia pastoris. Four variants, Ser-126, His-129, Arg-129 and Arg-145, all exhibited various degrees of altered binding of HBsAg to several monoclonal antibodies. Arg-145, a well-characterized immune escape mutant, and Arg-129 had the lowest binding capacities to all monoclonal antibodies as compared with other variants. Similar to Arg-145, the Arg-129 variant could be isolated from both vaccinated children and unvaccinated adults, thus representing a naturally occurring mutant with an altered 'a' determinant. Whether these 'a' determinant variants with altered antigenicity might gradually become major circulating strains, as a consequence of the immune pressure against the wild-type HBV created by vaccination, remains to be monitored.

High rate of hepatitis C virus infection in an isolated community: persistent hyperendemicity or period-related phenomena?

We investigated underlying risks for hyperendemic hepatitis C virus (HCV) infection among the 1853 inhabitants of a mountainous village in Eastern Taiwan with high prevalence of HCV and hepatitis B virus (HBV). Among the 80 selected adults, we found that having resided away from the village before 1985 was protective against HCV infection, while residing in the village after 1985 posed little risk for HCV infection to children and young adults < 30 years of age. Among the 559 school children 7 through 14 years of age, anti-HCV prevalence was 1.9%, and the HBV carrier rate was 29%. Following up 270 children 1 year later, we found that new HCV infection occurred in 0.74% and new or repeated HBV infection occurred in 6.5% of the children, indicating distinct transmission patterns between HBV and HCV. Children of anti-HCV-positive mothers were either anti-HCV-negative or were infected by distinct genotypes of HCV from those infecting their mothers; most married couples in whom both were infected, were infected by HCV of discordant genotypes, indicating negligible importance of sexual or vertical HCV transmission. A case-control study comparing 13 anti-HCV-positive and 53 anti-HCV-negative children showed that having received parenteral medication in local clinics was a significant risk for HCV infection. Our data indicate that, unlike the case of HBV, HCV transmission by vertical or sexual route, or through casual contact are extremely inefficient, and our data further suggest that HCV hyperendemicity is unlikely to persist as a result of the more stringent practice of parenteral precautions in nearly all aspects of daily life.

Transmission of hepatitis C virus in Taiwan: prevalence and risk factors based on a nationwide survey.

A nationwide community-based survey on hepatitis C virus (HCV) was carried out in seven townships in Taiwan. A total of 11,904 men aged 30-64 years were recruited for testing for antibodies against HCV (anti-HCV) by second-generation enzyme immunoassay. A total of 272 seropositive cases and 282 seronegative controls were interviewed to explore risk factors for HCV infection in the study areas. Spouses of 214 seropositive cases were identified to assess the concordance of seropositivity of anti-HCV between spouses; genotypes of HCV were also tested in 26 couples who were both seropositive. A significant geographic variation in seroprevalence of anti-HCV was observed in the study townships (1.6-19.6%). Blood transfusions, medical injections, acupuncture and tattooing were related to an increased anti-HCV seroprevalence showing multivariate-adjusted odds ratios of 8.6, 2.5, 3.1, and 2.2, respectively, with corresponding population attributable risk percentages of 25%, 57%, 16%, and 3%, respectively. The anti-HCV prevalence in spouses of index cases (24%) was significantly higher than that observed in the general population of the study areas (4%). However, a striking interspousal discrepancy in HCV genotypes (20/26 = 77%) was observed among both seropositive couples. Common exposures to medical injections and acupuncture were reported by 15 (58%) of these couples. This study identified some endemic areas of HCV infection in Taiwan. Iatrogenic factors were common vehicles for HCV infection, and a concordance of anti-HCV seropositivity between spouses may primarily be due to extrafamilial iatrogenic infectious sources in study areas.