HLA-DQB1, -DQA1, -DRB1 linkage disequilibrium and haplotype diversity in a Mestizo population from Guadalajara, Mexico.

HLA-DQB1, -DQA1, and -DRB1 genes were typed by polymerase chain reaction with sequence-specific primer (PCR-SSP) in 159 healthy volunteers from 32 families living in Guadalajara, Mexico. Three-locus genotype data from all family members were used to infer haplotypes in 54 unrelated individuals of the sample, from which estimate of segregating haplotype frequencies and linkage disequilibrium (LD) between loci were computed. Genotype distributions were concordant with Hardy-Weinberg expectations (HWE) for all three loci, and allele distributions were similar to the ones observed in other Latin-American populations. Of the 56 distinct three-site (DQB1-DQA1-DRB1) haplotypes observed in the sample, the five most common (i.e., with frequencies of five counts or more) were: *0302-*0301-*04, *0201-*0201-*07, *0301-*0501-*14, *0402-*0401-*08, and *0501-*0101-*01. These common three-locus haplotypes also contributed to the majority of the significant two-locus linkage disequilibria of these three sites.

Skin reflectance in the Han Chinese and Tibetan populations.

Genetic and environmental factors are involved in the determination of skin pigmentation in humans. With the recent development of statistical and genetic tools in mapping complex traits in humans, it is becoming feasible to utilize such methods in identifying genes involved in skin pigmentation. Furthermore, the use of new portable reflectance spectroscopy instruments such as the Photovolt ColorWalk colorimeter allows researchers to measure skin reflectance of a large number of subjects with ease and accuracy. We used a new portable instrument (Photovolt ColorWalk) to study the skin reflectance of 372 Han Chinese and 274 Tibetan individuals to establish background reflectance measurements of unexposed skin of the inner upper arm in these two populations. In addition, we explored the effect of various factors such as age and gender on skin reflectance.

Evidence of a sex-dependent association between the MSX1 locus and nonsyndromic cleft lip with or without cleft palate in the Chilean population.

Prior studies have implicated an involvement of the Msx1 homeobox gene in cleft palate in mice and its homolog in humans (called MSX1 in the HOX7 gene, located on chromosome 4). In this study we present evidence of a sex-dependent association between MSX1 and non-syndromic cleft lip/palate (NSCLP) in the Chilean population. The sample included 73 NSCLP cases, 37 from multiplex families (Mx), 36 from simplex families (Sx), and 87 controls. Polymerase chain reaction amplification of the MSX1 intragenic microsatellite (CA)n-sequence shows significant (p = 0.035) differences in the allele frequencies between NSCLP-Mx males and control males. These differences are mainly due to frequency differences in allele *2 (173 base pairs) among cases (21.9%) and controls (13.2%). When the NSCLP cases are subdivided by sex and positive family history (Mx versus Sx), the Mx males (27.8%) as well as the total NSCLP-Mx cases (25.7%) showed significantly higher frequencies of allele *2, compared to controls (11.4% and 13.2%, respectively). Analysis of the genotype data indicates that the relative risk for NSCLP is greater for persons carrying allele *2 (i.e., odds ratio [OR] larger than 1), reaching significance for all Mx cases (OR = 2.67; 95% confidence interval [CI], 1.10 to 6.52) and even more pronounced for Mx males (OR = 3.33; 95% CI, 1.08 to 10.32). Taken together, these findings support the hypothesis that the genetic variation at the MSX1 locus is a predisposing gene involved in sex-dependent susceptibility to clefting and that it also differentiates simplex from multiplex families.

Gender and treatment differences in knowledge, health beliefs, and metabolic control in Mexican Americans with type 2 diabetes.

PURPOSE: The purpose of this project was to describe metabolic control, knowledge, and health beliefs of Mexican Americans with type 2 diabetes. METHODS: The study site was Starr County, Texas, a border community located on the Rio Grande River and bordering northern Mexico. Of the total sample of 360 persons, 252 agreed to participate in this intervention study and were randomized either to the treatment group or the control group that waited 1 year to begin the intervention. RESULTS: The majority of individuals were Spanish-speaking females with a mean age of 54 years and a mean diabetes duration of 8 years. For those treated with diet only, males exhibited higher fasting blood glucose levels than females. Gender effects were seen for cholesterol level, with females exhibiting higher levels than males. Males expressed stronger perceptions of control and social support for diet. Bivariate relationships were found between acculturation and diabetes knowledge. The health belief subscales of control and impact on job together explained 16% of the variance in HbA1c values. CONCLUSIONS: Males and females held differing beliefs about ability to control their diabetes and degree of social support for diet. The impact of gender differences on ability to integrate diabetes self-care and on effectiveness of diabetes programs has not been determined but should be considered in future research.

Estimation of nonpaternity in the Mexican population of Nuevo Leon: a validation study with blood group markers.

A method for estimating the general rate of nonpaternity in a population was validated using phenotype data on seven blood groups (A1A2BO, MNSs, Rh, Duffy, Lutheran, Kidd, and P) on 396 mother, child, and legal father trios from Nuevo León, Mexico. In all, 32 legal fathers were excluded as the possible father based on genetic exclusions at one or more loci (combined average exclusion probability of 0.694 for specific mother-child phenotype pairs). The maximum likelihood estimate of the general nonpaternity rate in the population was 0.118 +/- 0.020. The nonpaternity rates in Nuevo León were also seen to be inversely related with the socioeconomic status of the families, i.e., the highest in the low and the lowest in the high socioeconomic class. We further argue that with the moderately low (69.4%) power of exclusion for these seven blood group systems, the traditional critical values of paternity index (PI > or = 19) were not good indicators of true paternity, since a considerable fraction (307/364) of nonexcluded legal fathers had a paternity index below 19 based on the seven markers. Implications of these results in the context of genetic-epidemiological studies as well as for detection of true fathers for child-support adjudications are discussed, implying the need to employ a battery of genetic markers (possibly DNA-based tests) that yield a higher power of exclusion. We conclude that even though DNA markers are more informative, the probabilistic approach developed here would still be needed to estimate the true rate of nonpaternity in a population or to evaluate the precision of detecting true fathers.

Symptom-related self-care of Mexican Americans with type 2 diabetes: preliminary findings of the Starr County Diabetes Education Study.

Starr County, Texas, a Texas-Mexico border community, was the site of a study involving culturally-appropriate education and group support for Mexican Americans with type 2 diabetes. Data were collected from 63 subjects on frequency of diabetes-related symptoms during the previous month and on self-care symptom treatments. On average, subjects were 57-year-old females, diagnosed with diabetes for 10 years, and exhibiting HbA1c levels of 12.5%. Almost 50% experienced excessive urination, excessive thirst, shakiness/nervousness, and numbness and/or tingling in their extremities. More than 50% of those who experienced symptoms did not view them as serious. Only one subject checked blood sugar levels when symptoms occurred. Significantly higher mean glycosylated hemoglobin levels were found for individuals who experienced dizziness and/or chest pain compared with those who did not. A variety of self-care treatments were employed, including over-the-counter medications and home remedies.

Complex segregation analysis of facial clefting in Chile.

Nonsyndromic cleft lip with or without cleft palate (CL/P) has an incidence of 1.5 per 1,000 live births in Chile, with 1.7 per 1,000 in males and 1.3 per 1,000 in females, which is nearly the same as the level found in Asian populations. The high rate of occurrence of CL/P in Chile is probably due to the presence of Amerindian genes in Chilean populations. Using the computer program PAP, a complex segregation analysis of CL/P was conducted for 67 multigeneration pedigrees from Chile, each ascertained from one affected proband. These pedigrees yielded 162 affected individuals and over 898 family members who were included in the analysis. The most parsimonious model of transmission indicated the presence of an autosomal dominant gene with reduced (20-25%) penetrance.

Boron levels in man: preliminary evidence of genetic regulation and some implications for human biology.

Boron is a ubiquitous constituent of man's external environment. Levels of the element in human blood reflect both acute and chronic exposure, usually as dietary intake (food and drinking water). There is an absolute requirement for boron in vascular plants but evidence for biological essentiality in animals (including man) is limited. A high body burden of the element may be harmful, especially to young animals (including human neonates). Information on boron deficiency is scanty. It has been proposed that boron contributes to living systems by acting indirectly as a proton donor and that it exerts a particular influence on cell membrane structure and function. The present study examines the variation in blood levels within and between human sibships and provides some support for the possibility that boron metabolism is subject to genetic regulation.

Blood lead concentrations and associated factors in residents of Monterrey, Mexico.

Data from interviews of 469 random subjects living in Monterrey, Nuevo León, México were analyzed to investigate factors associated with blood lead (PbB). The following criteria were considered: age, sex, residence zone, occupation, smoking, alcohol consumption, and the use of glazed pottery. Multiple linear regression analysis disclosed that PbB concentration was significantly higher in males, in residents of northeastern (NE) Monterrey, and in blue-collar workers. The highest atmospheric lead (PbA) concentrations of all Monterrey were also found in the NE, the zone that contains the greatest density of factories within the city. PbB and PbA means were significantly correlated (r = 0.964) with regard to the four urban zones considered. It is concluded that increased PbB level in specific categories is probably explained by exposure to PbA originating from industrial emissions.

Anticomplementary activity in serum samples from patients with acute parvovirus B19 infection.

Of 65 serum samples submitted for diagnostic purposes which proved to be anti-complementary by complement fixation test, 49 were parvovirus B19 IgM positive. Forty four of the 49 serum samples were from patients with arthropathy. Acute parvovirus B19 infection should be suspected when a patient has symptoms of disease of the joints and the serum is anticomplementary.

Gas exchange in a three-compartment lung model analyzed by forcing sinusoids of N2O.

A mathematical gas exchange model, using sinusoidal forcing functions of inert inspired gas (A. Zwart, R. C. Seagrave, and A. Van Dieren. J. Appl. Physiol. 41: 419-424, 1976), has been extended by us to include dead space (VD), a single alveolar compartment (VA) perfused with blood flow (Qp), and a shunt (Qs). In this new work we use N2O as the indicator gas in the mathematical model and in the experimental studies, in low enough concentrations [<6% (vol/vol)] to avoid anesthetic effects. Mathematical relationships between the inspired and expired N2O gas partial pressures, the blood gas N2O partial pressures, and their variation with forcing frequency are derived for a continuous ventilation uptake and a conventional anesthetic gas distribution model. We show that these gas and blood gas N2O relationships give direct derivation of cardiorespiratory parameters such as VA, Qp, the dead space-to-total ventilation ratio (VD/VT), and the shunt-to-total blood flow ratio (Qs/QT) without altering the subject's oxygenation and that they are essentially free from recirculation effects at high forcing frequencies > or = 2 min-1. Theoretical results from the model are presented for a wide range of forcing frequencies between 2 x 10(-2) and 10 min-1 (sinusoid periods 30-0.1 min), and these show that VA, Qp, and VD/VT can all be measured by N2O forcing frequencies > or = 1 min-1. We also present results from five animal studies, with an experimental inspired gas forcing frequency range of 0.125 to 2 min-1, which show qualitative agreement with the predictions of the continuous ventilation model. During these animal studies both mass spectrometric N2O respiratory gas measurements and intravascular polarographic arterial and mixed venous blood N2O partial pressure measurements were made, and examples of these in vivo measurements are presented, together with examples of the calculations derived from them.

An ultrasound survey of gallbladder disease among Mexican Americans in Starr County, Texas: frequencies and risk factors.

The Mexican-American population of south Texas has been shown previously to have elevated frequencies of gallbladder disease, based on medical history. In the present study, ultrasonography was employed to screen 1004 randomly selected individuals aged 15 to 74 years. Among women, the frequency of previous cholecystectomy was 10.0%; the frequency of stones on ultrasound was 12.2%. In men, the respective frequencies were 1.7% and 6.3%. Highest frequencies of gallbladder disease occurred among those aged 45 years or above: 40.2% and 19.2% among women and men, respectively. Non-insulin-dependent diabetes mellitus, obesity, and hypertension were also markedly elevated in this population. Overall, more than 40% of the population had either gallbladder disease, non-insulin-dependent diabetes, obesity, or hypertension. Among those older than 45 years, 70% had one or more of these chronic conditions. Examining the associations of gallbladder disease with other chronic diseases or measures of lipids, lipoproteins, and apolipoproteins demonstrates that factors predictive of or associated with cholecystectomy are different from those for gallstones by ultrasound. Diabetes and obesity show the strongest associations with cholecystectomy among women under 45 years (women with diabetes being 6.8 times as likely to have had a cholecystectomy than those without diabetes). Testing an extensive array of lipid-related measures resulted in no clear patterns, with the possible exception of alpha-lipoprotein and related measures. That the Mexican-American population is relatively young and experiencing extremely rapid growth indicates that the burden of chronic disease in general and gallbladder disease in particular will increase dramatically in the coming years.

Mortality of Mexican Americans with NIDDM. Retinopathy and other predictors in Starr County, Texas.

OBJECTIVE: To determine the rate and risk factors of mortality in a cohort of Mexican Americans with NIDDM. RESEARCH DESIGN AND METHODS: A cohort of 353 Mexican Americans with NIDDM were identified between 1981 and 1986. All individuals underwent extensive evaluations that included physical, historical, ophthalmological, and laboratory assessments. This cohort was followed prospectively for a mean of 8 yr. Follow-up included mortality surveillance, death certificate extraction, and a combination of annual and intermediate examinations. RESULTS: The cohort experienced 67 mortality events. One-third of all deaths were premature < 65 yr of age) and most often were attributed to diseases of the heart (60.0%). In no case was diabetes listed as the cause of death, although it was listed as a contributing cause in 25.5% of cases. Men had a higher mortality rate than women. In both sexes, baseline retinopathy was identified as an important predictor of subsequent mortality. Mortality was significantly elevated in those with nonproliferative retinopathy and even further elevated in those with proliferative disease (relative risks of > or = 4 for proliferative disease). CONCLUSIONS: Mexican Americans with NIDDM are experiencing premature and excessive mortality compared with the general population. The results clearly link microvascular complications with macrovascular disease, but this link is not explained by a more untoward profile of traditional cardiovascular risk factors. Retinopathy appears to serve as an important monitor of the progression of diabetes and when identified would warrant aggressive action to inhibit or slow the processes leading to subsequent mortality.

Characteristics of polymorphism at a VNTR locus 3' to the apolipoprotein B gene in five human populations.

We have analyzed the allele frequency distribution at the hypervariable locus 3' to the apolipoprotein B gene (ApoB 3' VNTR) in five well-defined human populations (Kacharis of northeast India, New Guinea Highlanders of Papua New Guinea, Dogrib Indians of Canada, Pehuenche Indians of Chile, and a relatively homogeneous Caucasian population of northern German extraction) by using the PCR technique. A total of 12 segregating alleles were detected in the pooled sample of 319 individuals. A fairly consistent bimodal pattern of allele frequency distribution, apparent in most of these geographically and genetically diverse populations, suggests that the ApoB 3' VNTR polymorphism predates the geographic dispersal of ancestral human populations. In spite of the observed high degree of polymorphism at this locus (expected heterozygosity levels 55%-78%), the genotype distributions in all populations (irrespective of their tribal or cosmopolitan nature) conform to their respective Hardy-Weinberg predictions. Furthermore, analysis of the congruence between expected heterozygosity and the observed number of alleles reveals that, in general, the allele frequency distributions at this locus are in agreement with the predictions of the classical mutation-drift models. The data also show that alleles that are shared by all populations have the highest average frequency within populations. These findings demonstrate the potential utility of highly informative hypervariable loci such as the ApoB 3' VNTR locus in population genetic research, as well as in forensic medicine and determination of biological relatedness of individuals.

Genetic structure of the populations migrating from San Luis Potosi and Zacatecas to Nuevo León in Mexico.

The Mexicans residing in the Monterrey metropolitan area in Nuevo León, Mexico, were grouped by generation and birthplace [Monterrey Metropolitan Area (MMA), San Luis Potosi (SLP), and Zacatecas (ZAC)] of the four grandparents to determine the extent of genetic variation within this population and the genetic differences, if any, between the natives living in the MMA and the immigrant populations from SLP and ZAC. Nine genetic marker systems were analyzed. The genetic distance analysis indicates that SLP and ZAC are similar to the MMA, irrespective of birthplace and generation. Gene diversity analysis (GST) suggests that more than 96% of the total gene diversity (HT) can be attributed to individual variation within the population. The genetic admixture analysis suggests that the Mexicans of the MMA, SLP, and ZAC, stratified by birthplace and generation, have received a predominantly Spanish contribution (78.5%), followed by a Mexican Indian contribution (21.5%). Similarly, admixture analysis, conducted on the population of Nuevo León and stratified by generation, indicates a substantial contribution from the MMA (64.6%), followed by ZAC (22.1%) and SLP (13.3%). Finally, we demonstrate that there is no nonrandom association of alleles among the genetic marker systems (i.e., no evidence of gametic disequilibrium) despite the Mestizo origin of this population.

Which measure of body fat distribution is best for epidemiologic research?

Multivariate associations were sought between risk factor levels (total cholesterol, high density lipoprotein (HDL) cholesterol, triglycerides, glucose, and systolic and diastolic blood pressures) and two sets of anthropometric variables (four circumferences and six skinfolds) to select a set of anthropometric indicators of body fat distribution that correlate most highly with risk of disease. Subjects were men (n = 285) and women (n = 672) from a study of gallbladder disease in a Mexican American population in Starr County, Texas, 1985-1986. The canonical correlations showed that circumferences (0.49-0.61) and skinfolds (0.42-0.60) were equally well correlated to risk factor levels independently of sex and age. Weights from the canonical analyses suggest that measurements at or above the waist and on the lower limb (thigh) are most heavily loaded toward risk (waist = highest risk; thigh = lowest risk). The simplest and most reliable index of body fat distribution for both sexes is the ratio of waist to thigh circumferences. The more commonly used waist/hip ratio proved more valid in women, but not in men. Simple skinfold indices of body fat distribution were more poorly correlated to risk factor levels than the corresponding circumference ratios. In women, body mass index and waist circumference by themselves did as well as body fat distribution indices in explaining variation in risk factors, suggesting the involvement of visceral fat in the body fat/body fat distribution disease relation.

A sensitive method for isolating Fusobacterium necrophorum from faeces.

The isolation of Fusobacterium necrophorum present in small numbers in heavily contaminated material such as faeces or soil is hampered by the lack of an efficient selective medium and by the high minimum infective dose of the organism. A sensitive method for the detection and isolation of faecal strains of F. necrophorum type A was based on the subcutaneous injection of faeces, suspended (5% w/v) in broth culture of Actinomyces (Corynebacterium) pyogenes or Staphylococcus aureus to increase fusobacterial infectivity, into mice pretreated with clostridial antitoxins. When necrobacillosis developed F. necrophorum was identified microscopically in tissue from the advancing edge of the lesion and isolated on a partly selective medium. The enhancement of fusobacterial infectivity produced by A. pyogenes and by S. aureus was high, but the latter was slightly the more efficient, enabling as few as 80 F. necrophorum organisms/g of faeces to be detected. Use of the method showed that 3 of 16 wallabies had F. necrophorum in their faeces at the time of examination. Numerous epidemiological applications are suggested.

Further observations on enhancement of the infectivity of Fusobacterium necrophorum by other bacteria.

It had already been shown with a single virulent strain (A42) of Fusobacterium necrophorum that suspension of the fusobacteria in sub-lethal doses of broth cultures of other bacteria reduced the minimum infective dose (greater than 10(6) organisms) for mice by subcutaneous inoculation, sometimes to less than 10 organisms. The present study extended the known range of bacteria with strong infectivity-enhancing properties to include Bacillus cereus, Klebsiella oxytoca and Staphylococcus aureus; and those with weaker effect to include Bacillus subtilis, 'Bacteroides melaninogenicus', Clostridium sporogenes, Pasteurella haemolytica, and Proteus mirabilis. The study also showed that five further virulent strains of F. necrophorum closely resembled A42 in respect of striking susceptibility to infectivity enhancement by Escherichia coli. Actinomyces (Corynebacterium) pyogenes and S. aureus. One further strain (A6) of F. necrophorum resembled A42 in respect of strong infectivity enhancement by A. pyogenes, S. aureus, B. cereus and K. oxytoca but differed from it and the other five strains in being only slightly affected by E. coli. This work was a necessary prelude to the development of a method, based on infectivity enhancement, for the detection and isolation of F. necrophorum present in small numbers in heavily contaminated material such as faeces.

Ethnicity determination by names among the Aymara of Chile and Bolivia.

The importance of surnames in genetic studies has been recognized for a century or so. While the ethnic affiliations of individuals are ordinarily established in genetic studies by admixture analysis based on gene frequencies, often there are implicit assumptions in these attempts that are difficult to validate in the absence of detailed ethnohistories. In northern Chile and western Bolivia, where genetic admixture has been known to occur among the Aymara Indians and Spanish Caucasoids, the naming pattern (parental patriand matrinyms) allowed us to classify individuals on the basis of the frequency of Aymara names into 9 'ethnic' groups. From a sample of 2525 individuals it is shown that admixture occurred in lineages nonrandomly, implying assortative mating of surnames. Admixture and genetic distance analysis on the basis of 31 genetic markers on approximately 1700 of these individuals reveals that there is a reasonable agreement of ethnic classification of individuals by name and phenotype data on genetic markers. The Aymara-named groups are shown to be predominantly Amerindian (89%) in their genetic profiles. Individuals whose current naming pattern is basically Spanish also exhibit a substantial fraction of genes of Amerindian origin (67%). Presence of some rare alleles not found in Amerindian or Spanish Caucasoids in the admixed groups suggest infiltration of Negroid genes in the past.

Response time of the EG&G 1420B detector in a coherent anti-Stokes Raman spectroscopy system.

Coherent anti-Stokes Raman spectroscopy measures combustion gas temperatures and molecular concentrations. This Letter reports the response times of our EG&G 1420B multichannel detector.