Risk ratios for obesity in families of obese African-American and Caucasian women

We examined age- and sex-standardized risk ratios (SRRs) in matched samples of 1,185 families of obese African-American and Caucasian women. Familial risk ratios increased with body mass index (BMI) of proband and BMI thresholds of relative. Ratios were higher in Caucasian than African-American families, apparently because Caucasian probands were more extreme relative to their population mean. Risk ratios for moderate obesity (BMI >/= 30) were around 2 for African-Americans and were a little higher in Caucasians. Ratios for extreme obesity (BMI >/= 40) ranged from 3 to 5 in African-Americans and from about 5 to 9 in Caucasians. Thin relatives were rare in families of both races. Risk ratios appear high enough in both racial groups to facilitate the identification of quantitative trait loci underlying common obesity phenotypes. The high population prevalence of obesity in African-American women will require particularly high selection thresholds to achieve risk ratios comparable to those for Caucasians. The scarcity of thin siblings in both groups will greatly increase the effort required in sample recruitment for discordant pair designs.     

Identification of common cystic fibrosis mutations in African-Americans with cystic fibrosis increases the detection rate to 75%.

Cystic fibrosis (CF)--an autosomal recessive disorder caused by mutations in CF transmembrane conductance regulator (CFTR) and characterized by abnormal chloride conduction across epithelial membranes, leading to chronic lung and exocrine pancreatic disease--is less common in African-Americans than in Caucasians. No large-scale studies of mutation identification and screening in African-American CF patients have been reported, to date. In this study, the entire coding and flanking intronic sequence of the CFTR gene was analyzed by denaturing gradient-gel electrophoresis and sequencing in an index group of 82 African-American CF chromosomes to identify mutations. One novel mutation, 3120+1G-->A, occurred with a frequency of 12.3% and was also detected in a native African patient. To establish frequencies, an additional group of 66 African-American CF chromosomes were screened for mutations identified in two or more African-American patients. Screening for 16 "common Caucasian" mutations identified 52% of CF alleles in African-Americans, while screening for 8 "common African" mutations accounted for an additional 23%. The combined detection rate of 75% was comparable to the sensitivity of mutation analysis in Caucasian CF patients. These results indicate that African-Americans have their own set of "common" CF mutations that originate from the native African population. Inclusion of these "common" mutations substantially improves CF mutation detection rates in African-Americans.     

Prepubertal Asians have less limb skeletal muscle.

Skeletal muscle mass in prepubertal Asian children has not been examined previously. The aims of this study were to test the hypotheses that 1) prepubertal Asians have less appendicular skeletal muscle (ASM) mass compared with African-Americans and Caucasians, and 2) ASM is less in prepubertal Asian girls compared with Asian boys. ASM was estimated by using dual-energy X-ray absorptiometry in healthy prepubertal girls (n = 170) and boys (n = 166). The results showed that, after adjusting for age, height, and body weight, 1) Asian girls and boys had less amounts of ASM than African-Americans (P < 0.001); 2) Asian girls had less amounts of ASM than Caucasian girls (P = 0.004); 3) there was a trend towards less ASM in Asian compared with Caucasian boys (P = 0.07); 4) and Asian girls had significantly less ASM than Asian boys (P < 0.001). This study indicates that skeletal muscle mass as a fraction of body weight is smaller in Asian compared with African-American and Caucasian children.     

A cross-sectional study of polycyclic aromatic hydrocarbon-DNA adducts and polymorphism of glutathione S-transferases among heavy smokers by race/ethnicity

Differences in lung cancer risk by race/ethnicity have been observed among smokers. To determine whether these observations might reflect differences in the formation of carcinogen-DNA adducts, we analysed blood specimens (n =151) collected from smokers who were recruited for possible participation in an antioxidant vitamin intervention study. Mononuclear cells were analysed for polycyclic aromatic hydrocarbon (PAH)-DNA adducts by competitive enzyme-linked immunosorbent assay. Genotypes of glutathione S-transferase M1 and P1 (GSTM1 and GSTP1), enzymes involved in the detoxification of PAH metabolites, were determined by polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism, respectively. GSTM1 was present in 65 out of 88 (73.4%), 16 out of 32 (50.0%) and 16 out of 29 (54.8%) of African-Americans, Caucasians and Latinos, respectively (p =0.022). Homozygosity for the GSTP1 codon 105 variant was found in 25.6%, 6.3% and 10.0% of African-Americans, Caucasians and Latinos, respectively (p =0.023). Regression analysis of the log-transformed adduct levels confirmed that Caucasian and Latino subjects had lower PAH-DNA adduct levels than African-American subjects, after adjustment for gender, education,α -tocopherol and β-carotene levels, and GSTM1 status. Further adjustment for age and current smoking habits had no impact on these findings. Although crude analysis suggested that the GSTM1-positive genotype may be associated with lower PAH-DNA levels in Caucasians (but not in African-Americans or Latinos), a formal test for interaction between GSTM1 and ethnicity was not significant. We found no association between adduct levels and GSTP1 genotype. Although the mechanism is unclear, ethnic differences in DNA damage levels may in part explain why African-Americans have higher lung cancer incidence rates than other ethnic groups.     

Neuroserpin polymorphisms and stroke risk in a biracial population: the stroke prevention in young women study

Background

Neuroserpin, primarily localized to CNS neurons, inhibits the adverse effects of tissue-type plasminogen activator (tPA) on the neurovascular unit and has neuroprotective effects in animal models of ischemic stroke. We sought to evaluate the association of neuroserpin polymorphisms with risk for ischemic stroke among young women.

Methods

A population-based case-control study of stroke among women aged 15–49 identified 224 cases of first ischemic stroke (47.3% African-American) and 211 age-matched control subjects (43.1% African-American). Neuroserpin single nucleotide polymorphisms (SNPs) chosen through HapMap were genotyped in the study population and assessed for association with stroke.

Results

Of the five SNPs analyzed, the A allele (frequency; Caucasian = 0.56, African-American = 0.42) of SNP rs6797312 located in intron 1 was associated with stroke in an age-adjusted dominant model (AA and AT vs. TT) among Caucasians (OR = 2.05, p = 0.023) but not African-Americans (OR = 0.71, p = 0.387). Models adjusting for other risk factors strengthened the association. Race-specific haplotype analyses, inclusive of SNP rs6797312, again demonstrated significant associations with stroke among Caucasians only.

Conclusion

This study provides the first evidence that neuroserpin is associated with early-onset ischemic stroke among Caucasian women.     

Classification and misclassification in sexing the Black femur by discriminant function analysis

Stepwise discriminant function analysis for sex assessment was applied to 130 North American Black femora. The measurements included femoral length and three midshaft dimensions likely to be preserved in archaeologically derived and forensic remains. The method correctly assigned sex for 76.4% of the sample (range 70.8–81.5%). This compares favorably with results achieved with other skeletal parts; it also compares favorably with results using the femur in sexing other racial groups. Among our other conclusions are: (1) a “general size factor” is one of major significance in correct classification and in misclassification of sex, and most misclassified individuals are anomalous for this factor; (2) the inconsistency in the relation between circumference and femoral length, which characterizes the remaining misclassified individuals, suggests that anomalous functional demands of body weight/musculature are at fault, and affect circumference more than length; and (3) discriminant function analysis of the same variables in Whites produced similar results, suggesting that sex overrides race in sex assessment; this was confirmed by cross-validating the predictive accuracy of Black discriminant function coefficients on White data, and vice versa.     

Technical, genetic, and ethical issues in screening and testing of African-Americans for hemochromatosis

To define more precisely populations in which hemochromatosis is frequent to rare, problems of racial classification are introduced, with particular reference to Europeans and African-Americans. Because the category "Caucasian" includes a multitude of dissimilar peoples, the categories Europeans and European-Americans have been substituted for Caucasian, which is archaic. The background of discrimination in sickle hemoglobin programs for African-Americans are then analyzed, including, discrimination by employers, life insurance, and selective mandatory testing. Discrimination and selective testing of African-American employees of the Lawrence Livermore Laboratory continues today without prior consent, as it has since the 1970s. Dissimilarities between the genetics of hemochromatosis in Europeans and their descendants, Africans, and African-Americans are briefly analyzed. Finally, it is concluded that because hemochromatosis is unlike sickle hemoglobin in that it is potentially preventable and treatable, prevention and treatment principles should apply as in other diseases. Furthermore, because hemochromatosis is so common in European-Americans, discrimination, if practiced, would not be selective for African-Americans.     

Evidence for a gene influencing heart rate on chromosome 4 among hypertensives

While mechanisms are poorly understood, resting heart rate has been shown to be a strong predictor of the risk of cardiovascular disease, cancer, and all-cause mortality. We performed a genome scan for quantitative trait loci influencing the resting heart rate among 962 Caucasians and 1,124 African-Americans in the Hypertension Genetic Epidemiology Network (HyperGEN), a multi-center study of genetic and environmental factors related to hypertension. The NHLBI Mammalian Genotyping Service typed a total of 391 anonymous microsatellite markers, spaced roughly equally throughout the genome. Within each race and sex, heart rate was adjusted for covariates, including age, age(2), study center, body mass index, beta-blocker use, alcohol consumption, smoking, number of city blocks walked per day, and number of hours watching television. Genome scans were performed using variance component linkage analysis as implemented by GENEHUNTER (version 2) for each race, using race-specific marker allele frequencies derived from random samples. The highest lod score detected in Caucasians was 2.14 on chromosome 4 (at 195.06 cM); a lod score of 1.14 was found at the same locus among the African-Americans, and a lod score of 3.18 resulted when the two racial groups were combined. Evidence was also found on chromosome 10 to support a recent report of an association between heart rate and the beta1 adrenergic receptor. The suggestive evidence for linkage found on chromosome 4 in both Caucasian and African-American hypertensive sib pairs indicates that further investigation on that region may be warranted to locate a gene influencing variability in resting heart rate.     

A cross-sectional study of polycyclic aromatic hydrocarbon-DNA adducts and polymorphism of glutathione S-transferases among heavy smokers by race/ethnicity.

Differences in lung cancer risk by race/ethnicity have been observed among smokers. To determine whether these observations might reflect differences in the formation of carcinogen-DNA adducts, we analysed blood specimens (n=151) collected from smokers who were recruited for possible participation in an antioxidant vitamin intervention study. Mononuclear cells were analysed for polycyclic aromatic hydrocarbon (PAH)-DNA adducts by competitive enzyme-linked immunosorbent assay. Genotypes of glutathione S-transferase M1 and P1 (GSTM1 and GSTP1), enzymes involved in the detoxification of PAH metabolites, were determined by polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism, respectively. GSTM1 was present in 65 out of 88 (73.4%), 16 out of 32 (50.0%) and 16 out of 29 (54.8%) of African-Americans, Caucasians and Latinos, respectively (p=0.022). Homozygosity for the GSTP1 codon 105 variant was found in 25.6%, 6.3% and 10.0% of African-Americans, Caucasians and Latinos, respectively (p=0.023). Regression analysis of the log-transformed adduct levels confirmed that Caucasian and Latino subjects had lower PAH-DNA adduct levels than African-American subjects, after adjustment for gender, education, alpha-tocopherol and beta-carotene levels, and GSTM1 status. Further adjustment for age and current smoking habits had no impact on these findings. Although crude analysis suggested that the GSTM1-positive genotype may be associated with lower PAH-DNA levels in Caucasians (but not in African-Americans or Latinos), a formal test for interaction between GSTM1 and ethnicity was not significant. We found no association between adduct levels and GSTP1 genotype. Although the mechanism is unclear, ethnic differences in DNA damage levels may in part explain why African-Americans have higher lung cancer incidence rates than other ethnic groups.     

Nasal contribution to breathing with exercise: effect of race and gender.

Because the nose acts as a filter to prevent penetration of toxic particles and gases to the lower respiratory tract, the route of breathing, oral vs. nasal, may be an important determinant of toxicant dose to the lungs. Using respiratory inductance plethysmography and a nasal mask fitted with flowmeter, we measured the nasal contribution to breathing at rest and during exercise (to 60% maximum workload) in healthy young adults (men/women = 11/11 and Caucasian/African-American = 11/11). We found that the nasal contribution to breathing is less during submaximal exercise in the Caucasians vs. African-Americans (e.g., at 60% maximum workload, mean nasal-to-total ventilation ratio = 0.40 +/- 0.21 and 0.65 +/- 0.24, respectively, P < 0.05). This difference is likely due to the African-Americans' ability to achieve higher maximal inspiratory flows through their nose than the Caucasians. Men also had a lesser nasal contribution to breathing during exercise compared with women. This is likely due to greater minute ventilations at any given percentage of maximum workload in men vs. women.     

Ethnic differences in cytokine gene polymorphisms: potential implications for cancer development

Differences in incidence and outcome of cancer among ethnic groups may be explained by biological and/or socio-economic factors. Genetic variations that affect chronic inflammation, a potentially important risk factor for carcinogenesis, may differ across ethnic groups. Such differences may help explain cancer disparities among these groups. Single nucleotide polymorphisms (SNPs) within cytokine genes can affect cytokine levels and the degree of inflammation. Associations between cancer and some cytokine SNPs have been suggested. However, these have not been consistently replicated among populations, suggesting that SNP function may differ according to ethnicity, or that SNPs alone do not completely account for regulation of inflammation. We examined seven polymorphisms in African-American (n = 294) and Caucasian (n = 299) newborns in Louisiana: IL1B-511C > T, IL1B-31T > C, IL1B + 3954C > T, IL1RN*2, IL10-1082G > A, IL10-592C > A, and TNF-308G > A. African-American newborns had significantly higher frequencies of IL1B-511T, IL1B-31C, IL10-1082A and IL10-592A alleles and complete linkage equilibrium between IL1B + 3954 and IL1B-31. In contrast, IL1B + 3954T, IL1RN*2, and TNF-308A were more frequent in Caucasian newborns and exhibited strong linkage disequilibrium between IL1B + 3954 and IL1B-31. All allelic frequencies were significantly different between groups. We hypothesize that these dissimilarities may contribute to differences in the inflammatory response and cancer incidence and mortality between African-Americans and Caucasians in Louisiana.     

Brief communication: Sex determination accuracy of the minimum supero-inferior femoral neck diameter in a contemporary rural Guatemalan population

One hundred and fourteen femora (75 male and 39 female) derived from a contemporary rural Guatemalan population were studied to test the ability of the minimum supero-inferior femoral neck diameter as a sex indicator. With the discriminant functions previously developed from North American modern populations, a maximum of only 36% correctly sexed femora was obtained, with correct percentages as low as 4%. A new discriminant function for the Guatemalan rural population is presented, with a total of 89.5% correctly classified individuals. It is suggested that poor physical growth of the rural Guatemalan population, due to a stressful environment, can explain part of the metric differences observed between the North American and rural Guatemalan populations.     

Hypothesis of Long-Term Outcome after Coronary Revascularization in Japanese Patients Compared to Multiethnic Groups in the US

Background

Ethnicity has a significant impact on coronary artery disease (CAD). This study investigated the long-term outcomes of Japanese patients undergoing revascularization compared with US patients belonging to multiple ethnic groups.

Methods and Results

We evaluated clinical outcomes, based on ethnicity, of patients included in the Coronary Revascularization Demonstrating Outcome (CREDO-Kyoto) and the Texas (US) Heart Institute Research Database (THIRDBase) registries. For the analysis, we included 8871 patients from the CREDO-Kyoto registry (median follow-up period [FU], 3.5 years; interquartile range [IQR], 2.6–4.3) and 6717 patients from the THIRDBase registry (FU, 5.2 years; IQR, 3.8–6.5) who underwent percutaneous coronary intervention or bypass surgery. Cox proportional hazard models were constructed to compare the adjusted long-term outcomes for each ethnic group. A total of 8871 Japanese, 5170 Caucasians, 648 African-Americans, 817 Hispanics, and 82 Asian-Americans were identified. When adjusted, Japanese patients had significantly better outcomes than US patients, classified by ethnicity (Caucasians: hazard ratio [HR], 1.56; 95% confidence interval [CI], 1.35–1.79; Hispanics: HR, 1.53; 95% CI, 1.22–1.93; African-Americans: HR, 2.03; 95% CI, 1.62–2.56), except for Asian-Americans (HR, 0.84; 95% CI. 0.38–1.89) who had outcomes similar to Japanese patients.

Conclusion

Our findings indicate better survival outcomes in re-vascularized Japanese CAD patients compared to major ethnic groups in the US, including Caucasian, Hispanic, and African-American CAD patients. The characteristics and outcomes of Japanese CAD patients were similar to those of Asian-Americans, despite the sample size limitations in the US dataset.     

Weight loss and race modulate nitric oxide metabolism in overweight women

Weight reduction is associated with a decrease in the risk of developing cardiovascular disease. We hypothesized that, given the central role of reactive oxygen and nitrogen species in vascular biology, changes in nitric oxide (NO) metabolism contribute to benefits of weight loss. In a controlled weight loss trial involving overweight (body mass index (BMI) = 27-30 kg/m(2)), otherwise healthy premenopausal Caucasian and African-American women, serum levels of nitrite and nitrate, as an index of NO production, and protein 3-nitrotyrosine and myeloperoxidase (MPO), as markers of inflammation, were determined. Testing was performed before and after reduction to normal body weight (BMI < 25) under standardized conditions, with controlled diet, and following 1 month of weight maintenance. After weight loss there was an increase in nitrite and nitrate, and levels were higher among African-American women relative to Caucasian counterparts. Whereas weight loss was associated with a decrease in 3-nitrotyrosine in Caucasian women, no change was observed among African-Americans. Furthermore, MPO levels increased in response to weight loss for African-Americans, but did not change in Caucasian women. These data indicate that vascular production of reactive nitrogen species can be modulated by race and weight loss and highlight important racial differences in these responses and are discussed in the context of risk for developing vascular disease.     

Comparison of factors affecting daily variation of blood pressure in Filipino-American and Caucasian nurses in Hawaii

Although several studies have examined differences in daily blood pressure variability between African-American and Caucasian groups in the United States, little is known about the blood pressure variation of other ethnic groups. This study examined the effects of emotional state, setting, posture, and ethnicity on the ambulatory blood pressure of female health care workers (nurses and nurse's aides) from 2 ethnic groups: Filipino-Americans (N = 38) and Caucasians (N = 22). Ambulatory blood pressure measurements were obtained at 15-min intervals during a typical work day. Participants reported in a diary their setting (work or home), posture, mood, and specific activity at each measurement. The effects of these factors and ethnicity were examined using analysis of variance (ANOVA). The results show that for all subjects blood pressure was higher at work (P < 0.05), while standing (P < 0.05), during reports of negative moods (anxiety, anger, or sadness) (P < 0.05), and while engaging in activities such as interacting with fellow staff members at work and “washing up” at home. However, the Filipino-American women reported negative moods more frequently than their Caucasian counterparts (P < 0.05), had a greater proportion of readings taken while standing at work, and reacted differently than the Caucasian women to some specific activities; for instance, their blood pressure was not elevated when doing household chores. These results suggest that the extent of blood pressure variation in daily life may depend upon cognitive processes which are influenced by the cultural background and emotional state of the individual. They further suggest that ethnicity has an important impact on blood pressure variation. Am J Phys Anthropol 106:373–383, 1998. © 1998 Wiley-Liss, Inc.     

Impact of cytokine and cytokine receptor gene polymorphisms on cellular immunity after smallpox vaccination

We explored associations between SNPs in cytokine/cytokine receptor genes and cellular immunity in subjects following primary smallpox vaccination. We also analyzed the genotype–phenotype associations discovered in the Caucasian subjects among a cohort of African-Americans. In Caucasians we found 277 associations (p < 0.05) between gene SNPs and inter-individual variations in IFN-α, IL-12p40, IL-1β, IL-2, and TNF-α secretion levels. A collection of SNPs in the IL1RN, IL2RB, IL4R, IL6, IL10RB, IL12A, and IL12RB2 genes had consistent associations among both Caucasians and African-Americans. A regulatory SNP (rs452204) in the IL1RN gene was significantly associated with higher levels of IL-2 secretion in an allele dose-dependent manner in both race groups (p = 0.05 for Caucasians and p = 0.002 for African-Americans). IL12RB2 polymorphism rs3790567 was associated with a dose-related decrease in IL-1β secretion (p = 0.009 for Caucasians and p = 0.01 for African-Americans). Our results demonstrate that variations in smallpox vaccine-induced cytokine responses are modulated by genetic polymorphisms in cytokine and cytokine receptor genes.     

Haplotype Frequency Distribution and Linkage Disequilibrium Analysis of Single Nucleotide Polymorphisms at the Human FMO3 Gene Locus

We analyzed flavin-containing monooxygenase 3 (FMO3) polymorphisms, haplotype structure, and linkage disequilibrium (LD) in 256 Han Chinese and 50 African-American individuals to compare their haplotype frequencies and LD with other world populations. For the Han Chinese, genotyping of three haplotype tag single nucleotide polymorphisms (E158K, V257M, and E308G) was performed by polymerase chain reaction (PCR)-restriction fragment length polymorphism. For the African-Americans, genotyping of all coding exons was performed by modified PCR-single strand conformational polymorphism. Haplotype frequencies, LD, and evolutionary rates were inferred and estimated computationally. There were significant differences in haplotype frequency distribution and LD pattern among Han Chinese, African-Americans, and other world populations. Four major haplotypes of Han Chinese were EVE, KVE, EME, and EVG. Two major haplotypes of African-Americans were EVE and KVE. We found that sites 158 and 257 are in significant LD in both populations. This is the first report comparing FMO haplotypes and LD of Han Chinese with African-Americans. The data presented here justify further pharmacogenetic studies for potentially optimizing recommended drug dosages and evaluating relationships with disease processes.     

Which Is Better: Holdout or Full-Sample Classifier Design?

Is it better to design a classifier and estimate its error on the full sample or to design a classifier on a training subset and estimate its error on the holdout test subset? Full-sample design provides the better classifier; nevertheless, one might choose holdout with the hope of better error estimation. A conservative criterion to decide the best course is to aim at a classifier whose error is less than a given bound. Then the choice between full-sample and holdout designs depends on which possesses the smaller expected bound. Using this criterion, we examine the choice between holdout and several full-sample error estimators using covariance models and a patient-data model. Full-sample design consistently outperforms holdout design. The relation between the two designs is revealed via a decomposition of the expected bound into the sum of the expected true error and the expected conditional standard deviation of the true error.     

ALARM CALLS OF THE EUROPEAN GROUND SQUIRREL SPERMOPHILUS CITELLUS AND THE TAURUS GROUND SQUIRREL S. TAURENSIS ENCODE INFORMATION ABOUT CALLER IDENTITY

ABSTRACT

Vocalizations of many mammalian species have been reported to encode information about caller identity. In this study, we analyzed 300 alarm calls from 10 free-living European Ground Squirrels Spermophilus citellus (30 per individual) and 300 alarm calls from 10 free-living Taurus Ground Squirrels S. taurensis (30 per individual), and tested the potential of these calls to encode information about the callers' identities. Discriminant analysis including all 10 European Ground Squirrel individuals correctly classified 98% of calls, and cross-validation reached a classification success of 97%. Correct classification of 98% and cross-validation of 98% was assigned when the analysis included only those individuals producing calls consisting of both elements (eight individuals). For the Taurus Ground Squirrel, correct classification was 95% and cross-validation 94% for all 10 animals. When only those individuals producing calls consisting of both elements were included (eight individuals), discriminant analysis led to 94% correct classification and cross-validation produced a classification success of 93%. These analyses demonstrate that the structure of alarm calls in these two closely related species is highly variable and that it has significant potential to encode information about caller identity.