Case-control study of association of maternal recall of diarrhea or use of antimicrobials in the periconceptional period and neural tube defects

In June 1995 a case-control study was initiated by the Texas Department of Health among Mexican American women residing in the fourteen counties of the Texas-Mexico border. Case-women had carried infants with neural tube defect. Control-women had given birth to infants without neural tube defects. The case-control protocol included a general questionnaire which elicited information regarding illnesses experienced and antibiotics taken from three months prior to conception to three months after conception. An assessment of the associations between periconceptional diarrhea and the risk of neural tube defects indicated that the unadjusted association of diarrhea and risk of neural tube defect was significant (OR = 3.3, CI = 1.4–7.6). The unadjusted association of use of oral antimicrobials and risk of neural tube defect was also significant (OR = 3.4, CI = 1.6–7.3). These associations persisted among women who had no fever during the periconceptional period and were present irrespective of folate intake. Diarrhea was associated with an increased risk of NTD independent of use of antimicrobials. The converse was also true; antimicrobials were associated with an increased risk of NTD independent of diarrhea. Further research regarding these potentially modifiable risk factors is warranted. Replication of these findings could result in interventions in addition to folate supplementation. ^

The association of HSV 1 and 2 with atherosclerosis defined by CRP level

A study of the association of Herpes simplex virus 1 and 2 exposure to early atherosclerosis using high C-reactive protein level as a marker was carried out in US born, non-pregnant, 20-49 year olds participating in a national survey between 1999 and 2004. Participants were required to have valid results for Herpes simplex virus 1 and 2 and C-Reactive Protein for inclusion. Cases were those found to have a high C-reactive protein level of 0.3-1 mg/dL, while controls had low to normal values (0.01-0.29 mg/dL). Overall, there were 1211 cases and 2870 controls. Mexican American and non-Hispanic black women were much more likely to fall into the high cardiac risk group than the other sex race groups with proportions of 44% and 39%, respectively. ^ Herpesvirus exposure was categorized such that Herpes simplex virus 1 and 2 exposure could be studied simultaneously within the same individual and models. The HSV 1+, HSV 2- category included the highest percentage (45.63%) of participants, followed by HSV 1-, HSV 2- (30.16%); HSV 1+, HSV 2+ (15.09%); and HSV 1-, HSV 2+ (9.12%) respectively. The proportion of participants in the HSV 1+, HSV 2- category was substantially higher in Mexican Americans (63%-66%). Further, the proportion in the HSV 1+, HSV 2+ category was notably higher in the non-Hispanic black participants (23%-44%). Non-Hispanic black women also had the highest percentage of HSV 1-, HSV 2+ exposure of all the sex race groups at 17%. ^ Overall, the unadjusted odds ratios for atherosclerotic disease defined by C-reactive protein with HSV 1-, HSV 2- as the referent group was 1.62 (95% CI 1.23-2.14) for HSV 1 +, HSV 2+; 1.3 (95% CI 1.10-1.69 for HSV 1+, HSV 2-; and 1.52 (95% CI 1.14-2.01). When the study was stratified into sex-race groups, only HSV 1+, HSV 2- in the Non-Hispanic white men remained significant (OR=1.6; 95% CI 1.06-2.43). Adjustment for selected covariates was made in the multivariate model for both the overall and sex-race stratified studies. High C-reactive protein values were not associated with any of the Herpesvirus exposure levels in either the overall or stratified analyses. ^

Association of self-reported physical activity and performance in the physical fitness assessment among Airmen

The U.S. Air Force, as with the other branches of military services, has physical fitness standards imposed on their personnel. These standards ensure a healthy and fit combat force. To meet these standards, Airmen have to maintain a certain level of physical activity in their lifestyle. Objective. This was a cross sectional (prevalence) study to evaluate the association of Airmen's self-reported physical activity and their performance in the Air Force Physical Fitness Assessment in 2007. Methods. The self-reported physical activity data were obtained from the Air Force Web Health Assessment (AF WEB HA), a web-based health questionnaire completed by the Airmen during their annual Preventive Health Assessment. The physical activity levels were categorized as having met or not having met the Centers for Disease Control and Prevention (CDC) and the American College of Sports Medicine (ACSM) physical activity recommendations. Physical Fitness scores were collected from the Air Force Fitness Management System (AFFMS), a repository of physical fitness test data. Results. There were 49,029 Airmen who answered the AF WEB HA in 2007 and also took their physical fitness test. 94.4% (n = 46,304) of Airmen met the recommended physical activity guidelines and 79.9% (n = 39,178) passed the fitness test. Total Airmen who both met the physical activity recommendations and passed the fitness test was 75.6% (n = 37,088). Airmen who did not meet the activity recommendations and also failed the fitness test totaled 635 or 1.3% of the study group. The Mantel-Haenszel Chi-Square analysis of the data on the activity levels and the physical fitness test relationship was the following χ2 = 18.52, df 1, and p = <0.0001. The Odds Ratio (OR) was 1.22 (95% CI 1.12, 1.34). Conclusion. The study determined that there was a positive association between Airmen's self-reported physical activity and their performance in the physical fitness assessment.^

The association of peer victimization and/or bullying perpetration and body dissatisfaction in elementary students from the healthy passages baseline study

This is the first U.S. study to investigate the association between peer victimization and/or bullying perpetration and body image dissatisfaction in American elementary school students. The study used data collected from the Healthy Passages baseline cohort of 5152 ethnically diverse fifth grade students from Alabama, Texas, and California. The overall prevalence of body dissatisfaction in our fifth grade sample was 50%. Students who were dissatisfied with their bodies were 23% more likely to be involved in peer victimization than students who were satisfied with their bodies (OR = 1.23; 95% CI = 1.02, 1.48). No significant associations were found between bullying status or bully-victim status and body dissatisfaction. Other factors that contributed significantly to a student's body image status were BMI, level of self-worth, level of household income, gender, pubertal timing and support received from adults (other than parents). It is noteworthy that those who were dissatisfied were heavier, came from lower income homes and were more likely to be male. Additional longitudinal studies are needed to confirm these associations, especially among large ethnically and socio-economically diverse samples. ^

Association of exogenous hormonal intake with the risk of development of hepatocellular carcinoma in women

Background. Primary liver cancer, the majority of which is hepatocellular carcinoma, is the third most common cause of mortality from cancer. It has one of the worst prognosis outcomes and an overall 5-year survival of only 5-6%. Hepatocellular carcinoma has been shown to have wide variations in geographic distribution and there is a marked difference in the incidence between different races and gender. Previously low-rate countries, including the US, have shown to have doubled the incidence of HCC during the past two decades. Even though the incidence of HCC is higher in males as compared to females, female hormones, especially estrogens have been postulated to have a role in the development of hepatocellular carcinoma on a molecular level. Despite the frequent usage of oral contraceptive pills (OCP) and previously, hormone replacement therapy (HRT), their role on HCC development has not been studied thoroughly. We aim to examine the association between exogenous hormone intake (oral contraceptives and post-menopausal hormone replacement therapy) and the development of HCC. Methods. This study is part of an ongoing hospital-based case-control study which is conducted at the Department of Gastrointestinal Oncology at The University of Texas M. D. Anderson Cancer Center. From January 2005 up to January 2008, a total of 77 women with pathologically confirmed hepatocellular carcinoma (cases) and 277 healthy women (controls) were included in the investigation. Information about the use of hormonal contraceptives, hormone replacement therapy and risk factors of hepatocellular cancer was collected by personal interview. Univariate and multivariate logistic regression analyses were done to estimate the crude odds ratios (OR) and adjusted odds ratios (AOR). Results. We found statistically significant protective effect for the use of HRT on the development of HCC, AOR=0.42 (95% CI, 0.21, 0.81). The significance was observed for estrogen replacement, AOR=0.43 (95% CI, 0.22, 0.83) and not for progesterone replacement, AOR=0.49 (95% CI, 0.10, 2.35). On the other hand, any hormonal contraceptive use, which encompasses oral contraceptive pills, implants and injections, did not show a statistical significance either in the crude OR=0.58 (95% CI, 0.33, 1.01) or AOR=0.56 (95% CI 0.26, 1.18). Conclusions. As corroborated by previous studies, HRT confers 58% HCC risk reduction among American women. The more important question of the association between hormonal contraceptives and HCC remains controversial. Further studies are warranted to explore the mechanism of the protective effect of HRT and the relationship between hormonal contraception and HCC.^

Association of processed red meat and prostate cancer stage in Mexican-Americans: A population based case-control study

Objective: The objective of this study is to investigate the association between processed and unprocessed red meat consumption and prostate cancer (PCa) stage in a homogenous Mexican-American population. Methods: This population-based case-control study had a total of 582 participants (287 cases with histologically confirmed adenocarcinoma of the prostate gland and 295 age and ethnicity-matched controls) that were all residing in the Southeast region of Texas from 1998 to 2006. All questionnaire information was collected using a validated data collection instrument. Statistical Analysis: Descriptive analyses included Student's t-test and Pearson's Chi-square tests. Odds ratios and 95% confidence intervals were calculated to quantify the association between nutritional factors and PCa stage. A multivariable model was used for unconditional logistic regression. Results: After adjusting for relevant covariates, those who consume high amounts of processed red meat have a non-significant increased odds of being diagnosed with localized PCa (OR = 1.60 95% CI: 0.85 - 3.03) and total PCa (OR = 1.43 95% CI: 0.81 - 2.52) but not for advanced PCa (OR = 0.91 95% CI: 1.37 - 2.23). Interestingly, high consumption of carbohydrates shows a significant reduction in the odds of being diagnosed with total PCa and advanced PCa (OR = 0.43 95% CI: 0.24 - 0.77; OR = 0.27 95% CI: 0.10 - 0.71, respectively). However, consuming high amounts of energy from protein and fat was shown to increase the odds of being diagnosed with advanced PCa (OR = 4.62 95% CI: 1.69 - 12.59; OR = 2.61 95% CI: 1.04 - 6.58, respectively). Conclusion: Mexican-Americans who consume high amounts of energy from protein and fat had increased odds of being diagnosed with advanced PCa, while high amounts of carbohydrates reduced the odds of being diagnosed with total and advanced PCa.^

Detection of nonrandom association of alleles from the distribution of the number of heterozygous loci in a sample.

The distribution of the number of heterozygous loci in two randomly chosen gametes or in a random diploid zygote provides information regarding the nonrandom association of alleles among different genetic loci. Two alternative statistics may be employed for detection of nonrandom association of genes of different loci when observations are made on these distributions: observed variance of the number of heterozygous loci (s2k) and a goodness-of-fit criterion (X2) to contrast the observed distribution with that expected under the hypothesis of random association of genes. It is shown, by simulation, that s2k is statistically more efficient than X2 to detect a given extent of nonrandom association. Asymptotic normality of s2k is justified, and X2 is shown to follow a chi-square (chi 2) distribution with partial loss of degrees of freedom arising because of estimation of parameters from the marginal gene frequency data. Whenever direct evaluations of linkage disequilibrium values are possible, tests based on maximum likelihood estimators of linkage disequilibria require a smaller sample size (number of zygotes or gametes) to detect a given level of nonrandom association in comparison with that required if such tests are conducted on the basis of s2k. Summarization of multilocus genotype (or haplotype) data, into the different number of heterozygous loci classes, thus, amounts to appreciable loss of information.

Association of retinoic acid receptor genes with meningomyelocele.

BACKGROUND: Neural tube defects (NTDs) occur in as many as 0.5-2 per 1000 live births in the United States. One of the most common and severe neural tube defects is meningomyelocele (MM) resulting from failed closure of the caudal end of the neural tube. MM has been induced by retinoic acid teratogenicity in rodent models. We hypothesized that genetic variants influencing retinoic acid (RA) induction via retinoic acid receptors (RARs) may be associated with risk for MM. METHODS: We analyzed 47 single nucleotide polymorphisms (SNPs) that span across the three retinoic acid receptor genes using the SNPlex genotyping platform. Our cohort consisted of 610 MM families. RESULTS: One variant in the RARA gene (rs12051734), three variants in the RARB gene (rs6799734, rs12630816, rs17016462), and a single variant in the RARG gene (rs3741434) were found to be statistically significant at p < 0.05. CONCLUSION: RAR genes were associated with risk for MM. For all associated SNPs, the rare allele conferred a protective effect for MM susceptibility.

Association of putative enteroaggregative Escherichia coli virulence genes and biofilm production in isolates from travelers to developing countries.

Enteroaggregative Escherichia coli (EAEC) is an emerging enteric pathogen that causes acute and chronic diarrhea among children, human immunodeficiency virus-infected patients, and travelers to developing regions of the world. The pathogenesis of EAEC strains involves the production of biofilm. In this study, we determined the association between presence of putative EAEC virulence genes and biofilm formation in 57 EAEC isolates (as defined by HEp-2 adherence) from travelers with diarrhea and in 18 EAEC isolates from travelers without diarrhea. Twelve nondiarrheagenic E. coli isolates from healthy travelers were used as controls. Biofilm formation was measured by using a microtiter plate assay with the crystal violet staining method, and the presence of the putative EAEC virulence genes aap, aatA, aggR, astA, irp2, pet, set1A, and shf was determined by PCR. EAEC isolates were more likely to produce biofilm than nondiarrheagenic E. coli isolates (P = 0.027), and the production of biofilm was associated with the virulence genes aggR, set1A, aatA, and irp2, which were found in 16 (40%), 17 (43%), 10 (25%), and 27 (68%) of the biofilm producers versus only 4 (11%), 6 (6%), 2 (6%), and 15 (43%) in non-biofilm producers (P = 0.008 for aggR, P = 0.0004 for set1A, P = 0.029 for aatA, and P = 0.04 for irp2). Although the proportion of EAEC isolates producing biofilm in patients with diarrhea (51%) was similar to that in patients without diarrhea (61%), biofilm production was related to the carriage of aggR (P = 0.015), set1A (P = 0.001), and aatA (P = 0.025). Since aggR is a master regulator of EAEC, the presence of aap (P = 0.004), astA (P = 0.001), irp2 (P = 0.0006), pet (P = 0.002), and set1A (P = 0.014) in an aggR versus an aggR-lacking background was investigated and was also found to be associated with biofilm production. This study suggests that biofilm formation is a common phenomenon among EAEC isolates derived from travelers with or without diarrhea and that multiple genes associated with biofilm formation are regulated by aggR.

Association of folate receptor (FOLR1, FOLR2, FOLR3) and reduced folate carrier (SLC19A1) genes with meningomyelocele.

BACKGROUND: Meningomyelocele (MM) results from lack of closure of the neural tube during embryologic development. Periconceptional folic acid supplementation is a modifier of MM risk in humans, leading toan interest in the folate transport genes as potential candidates for association to MM. METHODS: This study used the SNPlex Genotyping (ABI, Foster City, CA) platform to genotype 20 single polymorphic variants across the folate receptor genes (FOLR1, FOLR2, FOLR3) and the folate carrier gene (SLC19A1) to assess their association to MM. The study population included 329 trio and 281 duo families. Only cases with MM were included. Genetic association was assessed using the transmission disequilibrium test in PLINK. RESULTS: A variant in the FOLR2 gene (rs13908), three linked variants in the FOLR3 gene (rs7925545, rs7926875, rs7926987), and two variants in the SLC19A1 gene (rs1888530 and rs3788200) were statistically significant for association to MM in our population. CONCLUSION: This study involved the analyses of selected single nucleotide polymorphisms across the folate receptor genes and the folate carrier gene in a large population sample. It provided evidence that the rare alleles of specific single nucleotide polymorphisms within these genes appear to be statistically significant for association to MM in the patient population that was tested.

The association of genetic groups 1, 2, and 3 of Mycobacterium tuberculosis with pulmonary and extra-pulmonary tuberculosis

Objective. To investigate the association of the three major genetic groups of Mycobacterium tuberculosis with pulmonary and extra-pulmonary tuberculosis in clustered and non-clustered TB cases in the Houston area. ^ Study design. Secondary analysis of an ambi-directional study. ^ Study population. Three hundred fifty-eight confirmed cases of tuberculosis in the Houston that occurred between October 1995 and May 1997, who had been interviewed by the Houston T13 Initiative staff at Baylor College of Medicine, and whose isolates have had their DNA fingerprint and genetic group determined. ^ Exclusions. Individuals whose mycobacterial genotype was unknown, or whose data variables were unavailable. ^ Source of data. Laboratory results, patient interviews, and medical records at clinics and hospitals of the study population. ^ Results. In clustered cases, the majority of both, pulmonary and extra-pulmonary TB cases were caused by genetic group 1. Independent factors were assessed to determine the interactions that may influence the site of infection or increase the risk for one site or another. HIV negative males were protected against extra-pulmonary TB compared to HIV negative females. Individuals ages 1–14 years were at higher risk of having extra-pulmonary TB. Group 3 organisms were found less frequently in the total population in general, especially in extra-pulmonary disease. This supports the evidence in previous studies that this group is the least virulent and genetically distinct from the other two groups. Group 1 was found more frequently among African Americans than other ethnic groups, a trend for future investigations. ^ Among the non-clustered cases, group 2 organisms were the majority of the organisms found in both sites. They were also the majority of organisms found in African Americans, Caucasians, and Hispanics causing the majority of the infections at both sites. However, group 1 organisms were the overwhelming majority found in Asian/Pacific Islander individuals, which may indicate these organisms are either endemic to that area, or that there is an ethnic biological factor involved. This may also be due to a systematic bias, since isolates from individuals from that geographic region lack adequate copies of the insertion sequence IS6110, which leads to their placement in the non-clustered population. ^ The three genetic groups of Mycobacterium tuberculosis were not found equally distributed between sites of infection in both clustered and non-clustered cases. Furthermore, these groups were not distributed in the same patterns among the clustered and non-clustered cases, but rather in distinct patterns. ^

Linkage and association of candidate obesity genes in Mexican-Americans from Starr County, Texas

Obesity and related chronic diseases represent a tremendous public health burden among Mexican Americans, a young and rapidly-expanding population. This study investigated the impact of variation within eight candidate obesity genes, which include leptin (LEP), leptin receptor (LEPR), neuropeptide Y (NPY), NPYY1 receptor (NPYY1), glucagon-like peptide-1 (GLP-1), GLP-1 receptor (GLP1R), beta-3 adrenergic receptor (β3AR), and uncoupling protein (UCP1), on variation in human obesity status and/or quantitative traits related to obesity in Mexican Americans from Starr County, Texas. The Trp64Arg polymorphism within β3AR was typed in 820 random individuals and 240 pedigrees (N = 2,044). The Arg allele frequency was significantly greater in obese versus non-obese individuals (0.20 versus 0. 15, respectively). In addition, within the random sample, the Arg allele was associated with significantly greater body weight (p = 0.031) and body mass index (BMI, p = 0.008) than the Trp allele. In the family sample, the Trp64Arg locus was also linked to percent fat (p = 0.045) but not to body weight or BMI. No linkage between obesity, diabetes, hypertension, or gallbladder disease and the Trp64Arg mutation was observed in families using affected sib pair linkage analysis or the transmission disequilibrium test. Microsatellite markers proximate to the remaining seven genes were typed in 302 individuals from 59 families. Sib pair linkage analysis provided evidence for linkage between obesity and NPY within affected sibling pairs (p = 0.042; n = 170 pairs). NPY was also linked to weight (p = 0.020), abdominal circumference (p = 0.031), hip circumference (p = 0.012), DBP (p ≤ 0.005), and a composite measure of body mass/fat (p ≤ 0.048) in all sibling pairs (n = 545 pairs). Additionally, LEP was linked to waist/hip ratio (p ≤ 0.009), total cholesterol (p ≤ 0.030), and HDL cholesterol (p ≤ 0.026), and LEPR was linked to fasting blood glucose (p ≤ 0.018) and DBP (p ≤ 0.003). Subsequent to the linkage analyses, the NPY gene was sequenced and eight variant sites identified. Two variant sites (-880I/D and 69I/D) were typed in a random sample of 914 individuals. The 880I/D variant was significantly associated with waist/hip ratio (p = 0.035) in the entire sample (N = 914) and with BMI (p = 0. 031), abdominal circumference (p = 0.044), and waist/hip ratio (p = 0.041) in a non-obese subsample (BW < 30 kg/m2, n = 594). The 69I/D variant was a rare mutation observed in only one pedigree and was not associated with obesity or body size/mass within this pedigree. Results of this study indicate that variation at or near β3AR, LEP, LEPR, and NPY may exert effects which increase obesity susceptibility and influence obesity-related measures in this population. ^

PHENOTYPIC ASSOCIATION OF GENE AMPLIFICATION WITH MULTIPLE DRUG RESISTANCE IN VINCRISTINE RESISTANT CHINESE HAMSTER OVARY CELLS

Resistance of tumors to pharmacologic agents poses a significant problem in the treatment of human malignancies. This study overviews the scope of clinical resistance and focuses upon current research attempts toward investigation of the phenomenon of multidrug resistance (MDR).^ The objective of this investigation was to determine whether gene amplification had a role in the development of the MDR phenotype in Chinese hamster ovary cells (CHO) primarily selected for resistance to vincristine (VCR). A DNA fragment, previously shown to be amplified in two independently derived Chinese hamster cell lines exhibiting the MDR phenotype, was also amplified in VCR hamster lines. Sequences flanking this fragment were shown to contain coding information for a 4.3 kb transcript overproduced in VCR cells. These sequences were not enriched in double minute DNA preparations isolated from VCR cells. There was an approximately forty-fold increase in both the level of gene amplification and transcript overproduction in the VCR cell lines, independent of the level of primary resistance. This DNA amplification and overproduction of the 4.3 kb transcript was also demonstrated in CHO cells independently selected for resistance to Adriamycin and vinblastine.^ All the DNA sequences of two hamster cDNA clones containing 785 and 932 base pair inserts showed direct homology to the published mouse mdr sequences (about 90%). This sequence conservation held for only portions of the gene when the human mdr1 sequences were compared with those from either the mouse or hamster.^ Somatic cell hybrids, constructed between VCR CHO cells and sensitive murine cells, were used to determine whether there was a functional relationship between the chromosome bearing the amplified sequences and the MDR phenotype. Concordant segregation between vincristine resistance, the MDR phenotype, the presence of MDR-associated amplified sequences, overexpression of the mRNA encoded by these sequences, overexpression of the mRNA encoded by these sequences, and CHO chromosome Z1 was consistent with the hypothesis that there is an amplified gene on chromosome Z1 of the VCR CHO cells which is responsible for MDR in these cells. ^