Obesity Modulates the Association among APOE Genotype,Insulin, and Glucose in Men

Objective: Obesity, insulin resistance, and apolipoprotein E (APOE) genotype have all been associated with coronary heart disease. We examined the interaction between obesity and APOE genotype in determining fasting insulin and glucose levels. Research Methods and Procedures: From 1991 to 1995, 3799 subjects underwent a clinical examination and fasting insulin and glucose measurement. APOE genotypes were determined on 3500 participants. Participants taking oral hypoglycemic drugs or insulin preparations or with the rare APOE2/4 genotype were excluded. Finally, 2929 individuals were included in the present analysis. Results: In men, we observed a statistically significant interaction between obesity and APOE genotype on insulin and glucose level (p = 0.003 and 0.008, respectively). Obese men with the APOE4 genotype presented with higher levels of insulin and glucose than obese men in the other genotype groups. No association between genotype and insulin or glucose in nonobese men was observed. Obesity was associated with higher insulin levels in the three APOE genotypes groups, whereas obesity was directly associated with glucose in those with the APOE4 genotype. In women, the effect of interaction between APOE genotype and obesity on fasting insulin and glucose was not statistically significant. Obesity was associated with higher levels of fasting insulin and glucose. APOE genotype was not associated with insulin or glucose. Discussion: Obesity modulates the association between the APOE genotype and fasting insulin and glucose levels in men. Although weight control is important in all people, it may be especially important in APOE4 men to modify potentially elevated fasting insulin and glucose levels.     

American Indians with African Ancestry: Differential Fertility and the Complexities of Social Identity

Interethnic marriage represents a major trend in the demographic history of American Indians. While the majority of these unions involved Indian women and Caucasian men, a sizeable number occurred between Indians and African Americans. The children of these bicultural marriages were “mixed bloods” who in turn typically married non-Indians or other mixed bloods. Using data from the 1910 Census on American Indians in the United States and Alaska, this article explores why American Indians with African ancestry enjoyed high fertility. Differential rates of fertility among American Indians in the past were due to a number of underlying genetic, cultural, and environmental factors. By identifying these factors, the paradox of why Indian women with African heritage did so well in terms of fertility largely disappears. African admixture, however, greatly complicates Indian social identity.     

Phylogeography of Japanese Encephalitis Virus: Genotype Is Associated with Climate

The circulation of vector-borne zoonotic viruses is largely determined by the overlap in the geographical distributions of virus-competent vectors and reservoir hosts. What is less clear are the factors influencing the distribution of virus-specific lineages. Japanese encephalitis virus (JEV) is the most important etiologic agent of epidemic encephalitis worldwide, and is primarily maintained between vertebrate reservoir hosts (avian and swine) and culicine mosquitoes. There are five genotypes of JEV: GI-V. In recent years, GI has displaced GIII as the dominant JEV genotype and GV has re-emerged after almost 60 years of undetected virus circulation. JEV is found throughout most of Asia, extending from maritime Siberia in the north to Australia in the south, and as far as Pakistan to the west and Saipan to the east. Transmission of JEV in temperate zones is epidemic with the majority of cases occurring in summer months, while transmission in tropical zones is endemic and occurs year-round at lower rates. To test the hypothesis that viruses circulating in these two geographical zones are genetically distinct, we applied Bayesian phylogeographic, categorical data analysis and phylogeny-trait association test techniques to the largest JEV dataset compiled to date, representing the envelope (E) gene of 487 isolates collected from 12 countries over 75 years. We demonstrated that GIII and the recently emerged GI-b are temperate genotypes likely maintained year-round in northern latitudes, while GI-a and GII are tropical genotypes likely maintained primarily through mosquito-avian and mosquito-swine transmission cycles. This study represents a new paradigm directly linking viral molecular evolution and climate.     

FOXO 1a and FOXO 3a gene polymorphisms in association with metabolic syndrome

The prevalence and magnitude of childhood and adult obesity and diabetes are increasing dramatically. FOXO 1a and FOXO 3a will be evaluated in this study, in an effort to identify genetic polymorphisms in potential candidate genes that may be associated with body mass index (BMI), and metabolic syndrome (MS). Also to assess whether there is a relation between insulin sensitivity, and genotype, we will test the relation between fasting insulin, glucose, insulin resistance, insulin secretion and genotype.A total number of 248 presenting normal, overweight and obese individuals were recruited; 100 children and 148 adults of both sexes. They were divided by body mass index as follows, normal, overweight and obese. Lipid profile, fasting glucose and insulin HOMA-IR and HOMA-β index and RT-PCR for FOXO 1a and FOXO 3a were performed.An association was found among the studied group (children and adults) as regards foxo3a gene polymorphism and HOMA IR, HOMA B index and T-cholesterol (P = 0.022, 0.011 and 0.028, respectively), while there was only an association between LDL-C and foxo1a gene polymorphism among the studied group of children and adults (P = 0.023).In this study we demonstrated that FOXO3a mutant is correlated with HOMA-IR (marker of insulin resistance), HOMA-B index (marker of insulin secretion) and total cholesterol while as regards FOXO1a there was only an association between LDL cholesterol and mutant type of FOXO1a.     

Ancestry and Beginnings: The Early History of the American Society of Zoologists

SYNOPSIS. The American Society of Zoologists as we know it todaydescended from two immediate progenitors, the American MorphologicalSociety and the Western Branch of the American Society of Naturalists.The latter group was known during 1901 and 1902 as the Societyof American Zoologists. The two organizations formed the AmericanSociety of Zoologists at the American Society of Naturalists'1902 meeting in Washington, D.C. The American Society of Zoologistsfirst formed with two Branches, the Eastern and the Central.These two Branches merged into a single Society after the 1913meeting in Philadelphia.     

Association analysis of common variants in FOXO3 with type 2 diabetes in a South Indian Dravidian population

Recent studies have identified common variants in forkhead box O3 gene (FOXO3) to be strongly associated with longevity in different populations. But studies have not been carried out to analyse the role of common variants in FOXO3 with type 2 diabetes. Since type 2 diabetes is an age related disorder and FOXO proteins play an important role in the regulation of metabolism, we studied the role of common variants in FOXO3 for association with type 2 diabetes. The study was carried out in 994 type 2 diabetic samples and 984 normoglycemic control samples from a South Indian Dravidian population. In our analysis, we found that there was no association between any of the selected SNPs in FOXO3 with type 2 diabetes. Analysis of these SNPs with diabetes related biochemical and clinical parameters also did not reveal any significant association. Haplotype association of SNPs in FOXO3 with type 2 diabetes was observed, but the frequency of the haplotypes was considerably lower and they do not remain significant after correction for multiple testing. In conclusion, we did not observe any association of SNPs in FOXO3 with type 2 diabetes and related parameters suggesting an entirely different mechanism by which these SNPs influence longevity. However additional studies in other populations are required to completely rule out the association of common variants in FOXO3 with type 2 diabetes.     

Association of Genetic Ancestry with Breast Cancer in Ethnically Diverse Women from Chicago

Introduction

Non-Hispanic (nH) Black and Hispanic women are disproportionately affected by early onset disease, later stage, and with more aggressive, higher grade and ER/PR negative breast cancers. The purpose of this analysis was to examine whether genetic ancestry could account for these variation in breast cancer characteristics, once data were stratified by self-reported race/ethnicity and adjusted for potential confounding by social and behavioral factors.

Methods

We used a panel of 100 ancestry informative markers (AIMs) to estimate individual genetic ancestry in 656 women from the “Breast Cancer Care in Chicago” study, a multi-ethnic cohort of breast cancer patients to examine the association between individual genetic ancestry and breast cancer characteristics. In addition we examined the association of individual AIMs and breast cancer to identify genes/regions that may potentially play a role in breast cancer disease disparities.

Results

As expected, nH Black and Hispanic patients were more likely than nH White patients to be diagnosed at later stages, with higher grade, and with ER/PR negative tumors. Higher European genetic ancestry was protective against later stage at diagnosis (OR 0.7 95%CI: 0.54–0.92) among Hispanic patients, and higher grade (OR 0.73, 95%CI: 0.56–0.95) among nH Black patients. After adjustment for multiple social and behavioral risk factors, the association with later stage remained, while the association with grade was not significant. We also found that the AIM SNP rs10954631 on chromosome 7 was associated with later stage (p = 0.02) and higher grade (p = 0.012) in nH Whites and later stage (p = 0.03) in nH Blacks.

Conclusion

Non-European genetic ancestry was associated with later stage at diagnosis in ethnic minorities. The relation between genetic ancestry and stage at diagnosis may be due to genetic factors and/or unmeasured environmental factors that are overrepresented within certain racial/ethnic groups.     

Population genetics of Japanese monkeys: III. Ancestry and differentiation of local populations

Genetic variability in local populations of the Japanese macaque (Macaca fuscata) was quantified by the proportion of polymorphic loci (P_poly) and the average heterozygosity per individual ( ) from the starch- and polyacrylamide-gel electrophoreses of blood proteins controlled by 32 independent genetic loci. P_poly averaged 13.6% and 2.1%, the values being at lower level compared with other mammalian species. Geographical distribution of the genetic variations was not uniform in the whole species but its local differentiation was remarkable. Genetic variability tended to be lower in the southern localities, especially in the southernmost island of Yaku, than in the central and northern localities. The genetic distance and the principal component analyses showed that the most divergent local populations were the population in the Shimokita peninsula at the northernmost distribution area of the species and the populations on the Yaku island at the southernmost. The most contributory loci to the genetic divergence were the PGM-II, Gc, and Hb-β, the variant allele at the first locus being concentrated in the Yaku island, in the Shimokita peninsula, and in the easternmost Boso peninsula, and the variant allele at the latter two loci having high frequencies in the Shimokita and the Izu peninsulas. The Hennigian cladistic analysis, for which the Chinese rhesus macaque (M. mulatta) was used as the outgroup, revealed that the number of presence of derived (apomorphic) alleles was conspicuously smaller in southern islet populations than in central and northern populations, whereas any areal tendency was not recognized in the number of loss of ancestral (plesiomorphic) alleles. The observed distribution pattern that the plesiomorphic variant allele at the PGM-II locus concentrated only in the peripheral (southernmost, northernmost, and easternmost) ranges of the species, would indicate, as a possibility, the occurrence of two or more waves of immigration of ancestors of the present-day Japanese macaque from the Asian continent.     

Longer and Shorter Forms of Sendai Virus C Proteins Play Different Roles in Modulating the Cellular Antiviral Response

The Sendai virus (SeV) C gene codes for a nested set of four C proteins that carry out several functions, including the modulation of viral RNA synthesis and countering of the cellular antiviral response. Using mutant C genes (and in particular a C gene with a deletion of six amino acids present only in the larger pair of C proteins) and recombinant SeV carrying these mutant C genes, we find that the nested set of C proteins carry out a nested set of functions. All of the C proteins interdict interferon (IFN) signaling to IFN-stimulated genes (ISGs) and prevent pY701-Stat1 formation. However, only the larger C proteins can induce STAT1 instability, prevent IFN from inducing an antiviral state, or prevent programmed cell death. Remarkably, interdiction of IFN signaling to ISGs and the absence of pY701-Stat1 formation did not prevent IFN-alpha from inducing an anti-Vesicular stomatitis virus (VSV) state. It is possible that IFN-alpha signaling to induce an anti-VSV state can occur independently of the well-established Jak/Stat/ISGF3 pathway and that it is this parallel pathway that is targeted by the longer C proteins.     

Trans-Ethnical Shift of the Risk Genotype in the CETP I405V with Longevity: A Chinese Case-Control Study and Meta-Analysis

Background

The I405V polymorphism of the cholesteryl ester transfer protein gene (CETP) has been suggested to be a protective factor conferring longevity in Ashkenazi Jews, although findings in other races are not supportive. This paper describes a case-control study and a meta-analysis conducted to derive a more precise estimation of the association between CETP 405V and longevity.

Methods

We enrolled 1,021 ethnic Han Chinese participants (506 in the longevity group and 515 controls), then performed a meta-analysis that integrated the current study and previously published ones. Pooled odds ratios (OR) were calculated for allele contrasts, dominant and recessive inheritance models to assess the association between CETP 405V and longevity according to the ethnic stratification.

Results

Our case-control data indicated that CETP 405V is a longevity risk allele in all genetic models (P _additive=0.008; P _dominant=0.008, OR_dominant=0.673; P _recessive=0.017, OR_recessive=0.654) after adjustment for the apolipoprotein E (APOE) ε4 allele, body mass index and high-density lipoprotein cholesterol. A synergy was detected between 405V and APOE ε4 (P=0.001, OR=0.530). Eight studies were eligible for meta-analysis, which confirmed 405V is the risky allele against longevity in all genetic models: allele contrasts (OR=0.81, 95%CI=0.74-0.88), dominant model (OR=0.72, 95%CI=0.64-0.82) and recessive model (OR=0.80, 95%CI=0.67-0.96). After ethnic stratification, 405V remained a risk allele in East Asians but no significant association was found in Europeans or white Americans.

Conclusion

Our case-control study suggests CETP 405V as a risk allele against longevity in Chinese. The meta-analysis suggests the involvement of CETP 405V is protective in Ashkenazi Jews but is a risk allele against longevity in the East Asian (Chinese) population.     

Prevalence of Sexual Victimization and Correlates of Forced Sex in Japanese Men Who Have Sex with Men

Studies of men who have sex with men (MSM) in diverse geographic and cultural contexts have identified health challenges affecting this population. MSM might be particularly vulnerable to sexual victimization and forced sex. The aim of this research study was to examine prevalence of sexual victimization and correlates of forced sex among Japanese MSM. We recruited a sample of 5,731 Japanese MSM who completed an internet-administered survey. Participants reported on history of different types of sexual victimization, unprotected anal sex, other health risk behaviors, exposure to gay-related teasing and bullying, depression, and suicidality. Over one-fifth of the sample (21.4%) reported experiencing at least one form of sexual victimization, and 8.7% reported a history of forced sex. MSM who had ever experienced forced sex were significantly more likely to report experiencing psychological risks (depression OR = 1.55, 95% CI = 1.28–1.89; attempted suicide OR = 2.25, 95% CI = 1.81–2.81; other forms of bullying OR = 1.38, 95% CI = 1.13–1.68) and other behavioral risks (unprotected anal sex OR = 1.56, 95% CI = 1.29–1.90; sex venue attendance OR = 1.27, 95% CI = 1.04–1.54; methamphetamine use OR = 1.57, 95% CI  = 1.05–1.36), compared to MSM who had not experienced forced sex. Efforts to develop holistic and integrated health services for Japanese MSM are warranted, particularly related to psychosocial determinants of HIV prevention. However, due to cultural factors that emphasize familial and social relations and that stigmatize same-sex behavior, Japanese MSM might experience challenges to seeking social support and health services. Interventions must be provided in safe and non-judgmental settings where Japanese MSM feel comfortable disclosing their health and social support needs.     

Association of Mitochondrial DNA Haplogroups with Exceptional Longevity in a Chinese Population

Background

Longevity is a multifactorial trait with a genetic contribution, and mitochondrial DNA (mtDNA) polymorphisms were found to be involved in the phenomenon of longevity.

Methodology/Principal Findings

To explore the effects of mtDNA haplogroups on the prevalence of extreme longevity (EL), a population based case-control study was conducted in Rugao – a prefecture city in Jiangsu, China. Case subjects include 463 individuals aged ≥95 yr (EL group). Control subjects include 926 individuals aged 60–69 years (elderly group) and 463 individuals aged 40–49 years (middle-aged group) randomly recruited from Rugao. We observed significant reduction of M9 haplogroups in longevity subjects (0.2%) when compared with both elderly subjects (2.2%) and middle-aged subjects (1.7%). Linear-by-linear association test revealed a significant decreasing trend of N9 frequency from middle-aged subjects (8.6%), elderly subjects (7.2%) and longevity subjects (4.8%) (p = 0.018). In subsequent analysis stratified by gender, linear-by-linear association test revealed a significant increasing trend of D4 frequency from middle-aged subjects (15.8%), elderly subjects (16.4%) and longevity subjects (21.7%) in females (p = 0.025). Conversely, a significant decreasing trend of B4a frequency was observed from middle-aged subjects (4.2%), elderly subjects (3.8%) and longevity subjects (1.7%) in females (p = 0.045).

Conclusions

Our observations support the association of mitochondrial DNA haplogroups with exceptional longevity in a Chinese population.     

No Correlation between PNPLA3 rs738409 Genotype and Fatty Liver and Hepatic Cirrhosis in Japanese Patients with HCV

Background

Hepatitis C virus (HCV) infection is associated with the development of cirrhosis and hepatocellular carcinoma and is also related to fatty change of the liver. Variation in patatin-like phospholipase domain-containing 3 (PNPLA3) gene is associated with disease progression in nonalcoholic fatty liver disease (NAFLD). Recent reports have suggested that PNPLA3, IL28B and TLR4-associated single nucleotide polymorphisms (SNPs) may have an impact on hepatic steatosis or fibrosis in patients with chronic HCV infection.

Methods and Findings

Four SNPs (PNPLA3 rs738409, TLR4 rs4986790, TLR4 rs4986791, IL28B rs8099917) were identified in Japanese patients infected with HCV. We examined the association between the distribution of these SNP alleles and fatty change of the liver or existence of hepatic cirrhosis diagnosed by ultrasonography, one of the widely accessible and easy-to-use methods. PNPLA3 rs738409 G-allele and IL28B rs 8099917 minor allele were found in 70.0% and 31.1%, respectively. These two TLR4 SNPs were uniform in Japanese. Fatty change of the liver developed independent of the abscence of hepatic cirrhosis on sonographic findings and younger age. Hepatic cirrhosis was associated with a higher aspartate aminotransferase/platelet ratio index (APRI), no fatty change of the liver, higher BMI and higher AFP levels. No association between PNPLA3 rs738409/IL28B rs8099917 genotypes and hepatic steatosis or liver fibrosis was observed.

Conclusions

According to ultrasound examinations, no association between PNPLA3 rs738409 genotype and fatty change of the liver or hepatic cirrhosis was found in Japanese patients infected with HCV. Together, our results suggested that the mechanism of hepatic steatosis underlying HCV infection might differ from that of NAFLD and should be explored.     

Human Papillomavirus Genotype Distribution in Czech Women and Men with Diseases Etiologically Linked to HPV

Background

The HPV prevalence and genotype distribution are important for the estimation of the impact of HPV-based cervical cancer screening and HPV vaccination on the incidence of diseases etiologically linked to HPVs. The HPV genotype distribution varies across different geographical regions. Therefore, we investigated the type-specific HPV prevalence in Czech women and men with anogenital diseases.

Methods

We analyzed 157 squamous cell carcinoma samples, 695 precancerous lesion samples and 64 cervical, vulvar and anal condylomata acuminate samples. HPV detection and typing were performed by PCR with GP5+/6+ primers, reverse line blot assay and sequencing.

Results

Thirty different HPV genotypes were detected in our study, HPV 16 being the most prevalent type both in precancerous lesions (45%) and squamous cell carcinomas (59%). In benign lesions, HPV 6 (72%) was the most common type. Altogether, 61% of carcinoma samples and 43% of precancerous lesion samples contained HPV 16 and/or 18. The presence of HPV types related to the vaccinal ones (HPV 31, 45, 33, 52, 58) were detected in 16% of carcinoma samples and 18% of precancerous lesion samples. HPV 16 and/or 18 were present in 76% of cervical cancer samples, 33% of CIN1, 43% CIN2 and 71% of CIN3 samples. HPV types 6 and/or 11 were detected in 84% samples of condylomata acuminate samples.

Conclusions

The prevalence of vaccinal and related HPV types in patients with HPV-associated diseases in the Czech Republic is very high. We may assume that the implementation of routine vaccination against HPV would greatly reduce the burden of HPV-associated diseases in the Czech Republic.     

Possible Association of APOE Genotype with Working Memory in Young Adults

Background

Possession of the ε4 allele of the Apolipoprotein E (APOE) gene is associated with an increased risk of Alzheimer’s disease. Early adult life effects of ε4 are less well understood. Working memory has been relatively little studied (compared to episodic memory) in relation to APOE genotype despite its importance in cognitive functioning. Our hypothesis was that ε4 would lead to an impairment in working memory in young adults.

Methods

We studied working memory using a computerised n-back task in the Avon Longitudinal Study of Parents and Children (ALSPAC) at age 18. Data was available for 1049–1927 participants and for the 2- and 3-back versions of the task. Using multiple and multi-level regression controlling for important confounders we examined the association between APOE genotype on accuracy and reaction times.

Results

There was no evidence of a genotype effect on accuracy when the two difficulty levels were examined separately. There was some evidence to support a deleterious effect of the ε4 allele on n-back accuracy in the multi-level regression. There was weak evidence that the ε22 group were less accurate but the numbers were very low in this group. The ε34 group had faster reaction times than the reference ε33 group in all adjusted analyses but the ε44 group were only faster in the 3-back condition in multi-level analyses.

Conclusions

There was no evidence of benefit in ε4 carriers, but there was some evidence of a detrimental effect on working memory in this large study.