A genome scan for type 2 diabetes susceptibility loci in a genetically isolated population.

A total of 896 individuals of Ashkenazi Jewish descent were ascertained in Israel from 267 multiplex families, including 472 sib-pairs affected with type 2 diabetes. A genome-wide scan with average marker spacing of 9.5 cM revealed five regions on four chromosomes (4q, 8q, 14q, and 20q) that exhibited nominal evidence for linkage (P < 0.05). The highest observed nonparametric linkage Z score was 2.41 (equivalent to a logarithm of odds score of 1.26) at marker D4S1501. A maximal signal, with a Z score of 2.05, was observed on chromosome 20 near marker D20S195, and another on 20p near marker D20S103 (Z 1.80). A single marker on chromosome 8 (D8S593) and two adjacent markers on chromosome 14 (D14S749 and D14S605) also attained evidence of linkage. To explore the hypothesis that the signals on chromosomes 4 and 20 are differentially attributable to variation in BMI or age of onset, an ordered subset analysis was conducted. This analysis revealed that only when the families were ranked by BMI (in increasing order) did a subset attain nominal significance, and only for chromosome 4. The findings reported here lend credence to the hypothesis, now supported by four studies of Caucasian populations and most recently by a combined analysis of 1,852 pedigrees, that a type 2 diabetes susceptibility locus resides on chromosome 20q. This population, because of its unique genetic attributes, may facilitate identification of this and other genes contributing to type 2 diabetes.

Identification and functional analysis of novel human melanocortin-4 receptor variants.

Inactivation of the melanocortin-4 receptor (MC4-R) by gene-targeting results in mice that develop maturity-onset obesity, hyperinsulinemia, and hyperglycemia. These phenotypes resemble common forms of human obesity, which are late-onset and frequently accompanied by NIDDM. It is not clear whether sequence variation of the MC4-R gene contributes to obesity in humans. Therefore, we examined the human MC4-R gene polymorphism in 190 individuals ascertained on obesity status. Three allelic variants were identified, including two novel ones, Thr112Met and Ile137Thr. To analyze possible functional alterations, the variants were cloned and expressed in vitro and compared with the wild-type receptor. One of the novel variants, Ile137Thr, identified in an extremely obese proband (BMI 57), was found to be severely impaired in ligand binding and signaling, raising the possibility that it may contribute to development of obesity. Furthermore, our results also suggest that sequence polymorphism in the MC4-R coding region is unlikely to be a common cause of obesity in the population studied, given the low frequency of functionally significant mutations.

The epidemiology of early syphilis in Houston, Texas, 1994-1995.

BACKGROUND AND OBJECTIVES: Since 1990, rates of syphilis in the United States have steadily declined. However, the South still records disproportionately high rates of syphilis infection. GOAL: The objective of this study is to describe the epidemiology of early syphilis in Houston, TX, the largest urban center in the South, in 1994 and 1995. STUDY DESIGN: The study is cross-sectional and descriptive, and uses data collected by Disease Intervention Specialists on the Interview Form 73.54 from interviews with men and women diagnosed with early syphilis. RESULTS: Early syphilis in Houston is highly concentrated in a "belt" that extends north to south in a line just east of the city center. Although sex-specific rates of early syphilis are roughly equal, men are 3.5 times more likely than women to be diagnosed with primary syphilis, whereas women are nearly 2 times more likely than men to be diagnosed with secondary syphilis and 1.5 times more likely to be diagnosed with early latent syphilis. CONCLUSION: Routine surveillance data indicate that young, African-American men and women in Houston's inner-city neighborhoods are disproportionately affected by syphilis. Particular efforts must be made to reach women, who are detected and treated at later stages of the disease than men.

Dengue in Trinidad: a survey of knowledge, attitudes, practices and beliefs in two communities in Trinidad, West Indies

This study was conducted to test the Health Belief Model as it relates to dengue fever in two urban communities, namely Curepe and Woodbrook, Trinidad using a knowledge, attitude, practices and beliefs questionnaire and entomological investigations. The knowledge of dengue symptomatology, its prevention and control suggested a high level of awareness about dengue and its aetiological agents among residents of both commuities, but the connection between the vector Aedes aegypti (L.) and dengue fever transmission was poorly understood. The major determinants for cues to action were demographics, prevention of water treatment and garbage collection and disposal. Data from the present study gave clear indications of the need for health education programs, defining what garbage is and the further studies using the transtheoretical model of change (Prochaska Model). With these tools a holistic approach to vector control using community participation, health education and conventional vector control strategies may be adopted for the prevention and control of dengue and its vector. Ae. aegypti, on a sustained basis in Trinidad and, possibly, the Caribbean region.(AU)