Individuals Of Asian Ancestry Research Articles

Invisible no more: the intersectionality of Asian American immigrants experiences

ABSTRACT Violence against individuals of Asian ancestry is frequently overlooked and dismissed as a personal issue. This conceptual paper aims to critically analyze the roots of anti-Asian violence as a sociopolitical problem and investigate the systematic oppression that leads to the invisibility of Asian American experiences. To begin, we introduce two conventional paradigms that function as forms of systemic oppression, contributing to the marginalization of Asian American immigrants. Subsequently, we present the concept of intersectionality as an alternative paradigm for understanding the diverse experiences within the Asian American community. Furthermore, we offer suggestions for the training of social workers to better equip them to assist Asian American individuals and families who find themselves caught between the Black/White and Native/Alien binaries.

Molecular pathways identified from single nucleotide polymorphisms demonstrate mechanistic differences in systemic lupus erythematosus patients of Asian and European ancestry

Systemic lupus erythematosus (SLE) is a multi-organ autoimmune disorder with a prominent genetic component. Individuals of Asian-Ancestry (AsA) disproportionately experience more severe SLE compared to individuals of European-Ancestry (EA), including increased renal involvement and tissue damage. However, the mechanisms underlying elevated severity in the AsA population remain unclear. Here, we utilized available gene expression data and genotype data based on all non-HLA SNP associations in EA and AsA SLE patients detected using the Immunochip genotyping array. We identified 2778 ancestry-specific and 327 trans-ancestry SLE-risk polymorphisms. Genetic associations were examined using connectivity mapping and gene signatures based on predicted biological pathways and were used to interrogate gene expression datasets. SLE-associated pathways in AsA patients included elevated oxidative stress, altered metabolism and mitochondrial dysfunction, whereas SLE-associated pathways in EA patients included a robust interferon response (type I and II) related to enhanced cytosolic nucleic acid sensing and signaling. An independent dataset derived from summary genome-wide association data in an AsA cohort was interrogated and identified similar molecular pathways. Finally, gene expression data from AsA SLE patients corroborated the molecular pathways predicted by SNP associations. Identifying ancestry-related molecular pathways predicted by genetic SLE risk may help to disentangle the population differences in clinical severity that impact AsA and EA individuals with SLE.

Race and Ethnicity, Stage-Specific Mortality, and Cancer Treatment in Esophageal and Gastric Cancers: Surveillance, Epidemiology, and End Results (2000–2018)

Race and Ethnicity, Stage-Specific Mortality, and Cancer Treatment in Esophageal and Gastric Cancers: Surveillance, Epidemiology, and End Results (2000–2018)

Expression of Four Autophagy-Related Genes Accurately Predicts the Prognosis of Gastrointestinal Cancer in Asian Patients.

Gastrointestinal (GI) cancers are among the most fatal diseases in the world. Numerous studies have demonstrated the relationship between autophagy and development of gastrointestinal cancers. However, whether autophagy-related genes can predict prognosis of GI cancers in individuals of Asian ancestry has not been defined. This study, evaluated the prognostic value of autophagy-related genes in gastrointestinal cancer. Expression profile of autophagy-related genes for 296 gastrointestinal cancer patients of Asian ancestry was downloaded from the TCGA database (TCGA-LIHC, TCGA-STAD, TCGA-ESCA, TCGA-PAAD, TCGA-COAD, TCGA-CHOL, and TCGA-READ). The prognostic value of the autophagy-related genes was evaluated using univariate Cox, LASSO, and multivariate Cox regression analyses. The risk score of the autophagy-related gene signature was calculated to assess its predictive prognostic value for GI cancers. Forty-seven differentially expressed autophagy-related genes, in Asian patients with gastrointestinal cancers, were identified. Of the 47 genes, 4 were associated with prognosis of GI cancer (SQSTM1, BIRC5, NRG3, and CXCR4). A prognostic model for GI cancer, based on the expression of the above 4 genes in the training set, showed that cancer patients were stratified into high-risk and low-risk groups (P < 0.05). The utility of the model for overall survival (OS) of GI cancer patients was consistent across the entire set, training set, and test set (entire set: P = 4.568 × 10−4; train set: P = 5.718 × 10−3; test set: P = 3.516 × 10−2). The sensitivity and specificity of the ROC curve of the above prognostic model in predicting the 5-year prognosis of GI cancer was satisfactory (entire set: 0.728; train set: 0.727; test set: 0.733). Analysis of clinical samples validated the overexpression of the 4 genes (SQSTM1, BIRC5, NRG3, and CXCR4) in tumor tissues relative to paired normal tissues, consistent with bioinformatic findings. Expression of the 4 autophagy-related genes (SQSTM1, BIRC5, NRG3, and CXCR4) can accurately predict the prognosis of gastrointestinal tumors in Asian patients.

Improved prediction of fracture risk leveraging a genome-wide polygenic risk score

BackgroundAccurately quantifying the risk of osteoporotic fracture is important for directing appropriate clinical interventions. While skeletal measures such as heel quantitative speed of sound (SOS) and dual-energy X-ray absorptiometry bone mineral density are able to predict the risk of osteoporotic fracture, the utility of such measurements is subject to the availability of equipment and human resources. Using data from 341,449 individuals of white British ancestry, we previously developed a genome-wide polygenic risk score (PRS), called gSOS, that captured 25.0% of the total variance in SOS. Here, we test whether gSOS can improve fracture risk prediction.MethodsWe examined the predictive power of gSOS in five genome-wide genotyped cohorts, including 90,172 individuals of European ancestry and 25,034 individuals of Asian ancestry. We calculated gSOS for each individual and tested for the association between gSOS and incident major osteoporotic fracture and hip fracture. We tested whether adding gSOS to the risk prediction models had added value over models using other commonly used clinical risk factors.ResultsA standard deviation decrease in gSOS was associated with an increased odds of incident major osteoporotic fracture in populations of European ancestry, with odds ratios ranging from 1.35 to 1.46 in four cohorts. It was also associated with a 1.26-fold (95% confidence interval (CI) 1.13–1.41) increased odds of incident major osteoporotic fracture in the Asian population. We demonstrated that gSOS was more predictive of incident major osteoporotic fracture (area under the receiver operating characteristic curve (AUROC) = 0.734; 95% CI 0.727–0.740) and incident hip fracture (AUROC = 0.798; 95% CI 0.791–0.805) than most traditional clinical risk factors, including prior fracture, use of corticosteroids, rheumatoid arthritis, and smoking. We also showed that adding gSOS to the Fracture Risk Assessment Tool (FRAX) could refine the risk prediction with a positive net reclassification index ranging from 0.024 to 0.072.ConclusionsWe generated and validated a PRS for SOS which was associated with the risk of fracture. This score was more strongly associated with the risk of fracture than many clinical risk factors and provided an improvement in risk prediction. gSOS should be explored as a tool to improve risk stratification to identify individuals at high risk of fracture.

Genetics of Obesity in East Asians.

Obesity has become a public health problem worldwide. Compared with Europe, people in Asia tend to suffer from type 2 diabetes with a lower body mass index (BMI). Genome-wide association studies (GWASs) have identified over 750 loci associated with obesity. Although the majority of GWAS results were conducted in individuals of European ancestry, a recent GWAS in individuals of Asian ancestry has made a significant contribution to the identification of obesity susceptibility loci. Indeed, owing to the multifactorial character of obesity with a strong environmental component, the revealed loci may have distinct contributions in different ancestral genetic backgrounds and in different environments as presented through diet and exercise among other factors. Uncovering novel, yet unrevealed genes in non-European ancestries may further contribute to explaining the missing heritability for BMI. In this review, we aimed to summarize recent advances in obesity genetics in individuals of Asian ancestry. We therefore compared proposed mechanisms underlying susceptibility loci for obesity associated with individuals of European and Asian ancestries and discussed whether known genetic variants might explain ethnic differences in obesity risk. We further acknowledged that GWAS implemented in individuals of Asian ancestries have not only validated the potential role of previously specified obesity susceptibility loci but also exposed novel ones, which have been missed in the initial genetic studies in individuals of European ancestries. Thus, multi-ethnic studies have a great potential not only to contribute to a better understanding of the complex etiology of human obesity but also potentially of ethnic differences in the prevalence of obesity, which may ultimately pave new avenues in more targeted and personalized obesity treatments.

Genome-wide association study identifies new loci for albuminuria in the Japanese population

BackgroundUrinary albumin excretion (UAE) is a risk factor for cardiovascular diseases, metabolic syndrome, chronic kidney disease, etc. Only a few genome-wide association studies (GWAS) for UAE have been conducted in the European population, but not in the Asian population. Here we conducted GWAS and identified several candidate genes harboring single nucleotide polymorphisms (SNPs) responsible for UAE in the Japanese population.MethodsWe conducted GWAS for UAE in 7805 individuals of Asian ancestry from health-survey data collected by Tohoku Medical Megabank Organization (ToMMo) and Iwate Tohoku Medical Megabank Organization (IMM). The SNP genotype data were obtained with a SNP microarray. After imputation using a haplotype panel consisting of 2000 genome sequencing, 4,962,728 SNP markers were used for the GWAS.ResultsEighteen SNPs at 14 loci (GRM7, EXOC1/NMU, LPA, STEAP1B/RAPGEF5, SEMA3D, PRKAG2, TRIQK, SERTM1, TPT1-AS1, OR5AU1, TSHR, FMN1/RYR3, COPRS, and BRD1) were associated with UAE in the Japanese individuals. A locus with particularly strong associations was observed on TSHR, chromosome 14 [rs116622332 (p = 3.99 × 10−10)].ConclusionIn this study, we successfully identified UAE-associated variant loci in the Japanese population. Further study is required to confirm this association.

Craniometric estimation of ancestry in Thai and Japanese individuals

ABSTRACT There are currently no forensic methods for distinguishing Thais from other individuals of Asian ancestry using craniometrics. Of foreigners visiting or living in Thailand, Japanese people predominate. Remains of Japanese soldiers from the Second World War were excavated in northern Thailand, and hundreds more are thought to have disappeared in this area and nearby countries. This research aims to develop new formulae for ancestry estimation of skulls suspected to be Thai or Japanese. This was achieved by measuring 440 Thai and Japanese skulls. Stepwise discriminant analysis created four formulae. The first formula is for a complete skull, with predicted and correct classification accuracy of 89.3% and tested accuracy of 91.2%. The second formula, cranium only, gave 84.3% predicted and correct classification accuracy and tested accuracy of 85.3%. The third formula, for a male skull, gave predicted and correct classification accuracy of 92.0% and tested accuracy of 85.3%. The fourth formula, for a female skull, produced 89.8% predicted and correct classification accuracy and tested accuracy of 88.2%. Differentiating between Asian subgroups is challenging, but this study demonstrates the potential to distinguish Thai from Japanese individuals in forensic applications. It can be used to clarify ancestry of ‘Asian’ unclaimed bodies found in Thailand.

Overview on Keloid Disorder: Phenotypic Spectrum, Connective Tissue Pathology, and Treatment Development

Overview on Keloid Disorder: Phenotypic Spectrum, Connective Tissue Pathology, and Treatment Development

Variation in Maxillary Sinus Anatomy: Implications of Ostium Positioning on Health Disparities in Sinusitis

Over 30 million people are diagnosed with sinusitis annually, yet potential anatomical etiologies behind sinus infections remain poorly understood. Paranasal sinus drainage is mediated by mucociliary transport and gravity, but the human orthograde posture and superior positioning of the maxillary sinus (MS) ostia increase reliance on the mucociliary system. Moreover, previous research has suggested that regional differences in MS size and shape may contribute to disparities in sinusitis susceptibility. The purpose of this study was to examine overall MS size and shape, including MS ostium positioning, among three different ancestral groups, to assess potential impacts on drainage and infection risks. Employing CT scans (n=167) of crania from European, East Asian, and Equatorial African ancestries, we collected 28 3D coordinate landmarks per specimen. A total of 34 linear measurements of the MS and surrounding facial features were subsequently calculated and employed in multivariate analyses. MANOVA test results reveal significant differences between regional groups (Wilk’s λ = 0.807, p &lt; 0.0001) and between the sexes (Wilk’s λ = 0.813, p &lt; 0.0001), but no significant interaction between region and sex (Wilk’s λ = 0.971, p = 0.3223). ANOVA and Tukey‐Kramer test results indicate that Asians have both a significantly taller MS (F=15.4, p&lt;0.0001) and a significantly greater distance from the MS floor to the ostium (F=13.5, p&lt;0.0001) compared to Europeans and Africans. Further, a ratio of these two linear variables reveals that the MS floor‐to‐ostium distance constitutes a greater percentage of overall MS height in Asians (62%) than Europeans (60%) or Africans (59%). A canonical variate (CV) analysis of the 28 3D coordinate landmarks provides corroborative results, with CV1 accounting for 70.58% of total variance and separating Asians from Europeans and Africans. Morphologically, CV1 predominantly reflects a lower MS floor in Asians, while the relative superior‐inferior position of the MS ostium within the face appears similar across all ancestries. Cumulatively, these results suggest that both the taller sinus and greater MS floor‐to‐ostium distance in Asians are attributable to a more inferiorly positioned MS floor. As a greater distance from the MS floor to the ostium may lead to increased pressure on the mucociliary clearance, our results suggest that individuals of Asian ancestry may be at a greater risk for chronic sinusitis compared to those of European and African ancestries. Our study thus provides tentative evidence that there may be an anatomical etiology for chronic sinusitis despite an absence of anatomical defect. The increased risk for persistent inflammatory condition is also important since it has been accompanied with subsequent head and neck cancer diagnoses. Additional research into the prevalence of MS sinusitis in these populations is warranted to evaluate possible contributions to health disparities.Support or Funding InformationThis work is partially supported by a grant funded to Dr. Jamboor Vishwanatha by the Cancer Prevention and Research Institute of Texas (Award #: RP170301).

Incidence of hepatocellular carcinoma among older Americans attributable to hepatitis C and hepatitis B: 2001 through 2013.

In the United States, incidence and mortality rates of hepatocellular carcinoma (HCC) are increasing in older individuals. Chronic infection with hepatitis C virus (HCV) and hepatitis B virus (HBV) are important causes of HCC; however, the contribution of viral hepatitis to recent trends in HCC incidence among older Americans is unclear. Data from the Surveillance, Epidemiology, and End Results-Medicare linkage (SEER-Medicare) for the years 2001 through 2013 were used to identify HCC cases among individuals aged ≥66years and Medicare files were used to assess the HCV and HBV status of these HCC cases. Age-standardized incidence rates of HCV-attributable, HBV-attributable, and HCV/HBV-unrelated HCC were estimated overall and by age group, sex, and race/ethnicity. The authors also calculated annual percent changes (APCs) in HCC incidence. Between 2001 and 2013, a total of 15,300 HCC cases occurred in this population. Overall HCC rates increased 43% from 16.3 to 23.3 per 100,000 population (APC, 3.40% per year), whereas HCV-attributable HCC rates nearly doubled from 4.2 to 8.2 per 100,000 population (APC, 5.62% per year). HCC rates increased more slowly for HBV-attributable HCC (1.3 to 1.8 per 100,000 population; APC, 3.17% per year) and HCV/HBV-unrelated HCC (11.3 to 14.1 per 100,000 population; APC, 2.35% per year). The percentage of HCC cases with evidence of HCV infection increased from 25.7% in 2001 through 2004 to 32.3% in 2011 through 2013, whereas the percentage with HBV remained stable at 8%. In 2013, higher rates for both HCV-attributable and HBV-attributable HCC were noted among individuals aged 66 to 75years, men, and individuals of Asian ancestry. Among Americans aged ≥66years, HCC rates increased rapidly between 2001 and 2013. Although HCV-attributable cases contributed substantially to this increase, rates of HBV-attributable and HCV/HBV-unrelated HCC also rose during this period.

Mandibulofacial dysostosis Guion-Almeida type caused by novel EFTUD2 splice site variants in two Asian children

Mandibulofacial dysostosis type Guion-Almeida (MFDGA) is a rare disease entity that results in congenital craniofacial anomalies that are caused by abnormal development of the first and second pharyngeal arches. MFDGA is characterized by malar and mandibular hypoplasia, microcephaly, developmental delay, dysplastic ears, and a distinctive facial appearance. Extracraniofacial malformations include esophageal atresia, congenital heart disease, and radial ray abnormalities. Heterozygous mutations in the elongation factor Tu GTP-binding domain containing 2 (EFTUD2) gene have been shown to result in MFDGA. To date, there have been a total of 108 individuals reported in the literature, of whom 95 patients have a confirmed EFTUD2 mutation. The majority of individuals reported in the literature have been of White ethnic origin. Here, we report two individuals of Asian ancestry with MFDGA, each harboring a novel, pathogenic splice site variant in EFTUD2.

Meta-analysis of Genome-Wide Association Studies Identifies Novel Loci Associated With Optic Disc Morphology.

Primary open-angle glaucoma is the most common optic neuropathy and an important cause of irreversible blindness worldwide. The optic nerve head or optic disc is divided in two parts: a central cup (without nerve fibers) surrounded by the neuroretinal rim (containing axons of the retinal ganglion cells). The International Glaucoma Genetics Consortium conducted a meta-analysis of genome-wide association studies consisting of 17,248 individuals of European ancestry and 6,841 individuals of Asian ancestry. The outcomes of the genome-wide association studies were disc area and cup area. These specific measurements describe optic nerve morphology in another way than the vertical cup-disc ratio, which is a clinically used measurement, and may shed light on new glaucoma mechanisms. We identified 10 new loci associated with disc area (CDC42BPA, F5, DIRC3, RARB, ABI3BP, DCAF4L2, ELP4, TMTC2, NR2F2, and HORMAD2) and another 10 new loci associated with cup area (DHRS3, TRIB2, EFEMP1, FLNB, FAM101, DDHD1, ASB7, KPNB1, BCAS3, and TRIOBP). The new genes participate in a number of pathways and future work is likely to identify more functions related to the pathogenesis of glaucoma.

Adiponectin receptor 1 (ADIPOR1) rs1342387 polymorphism and risk of cancer: a meta-analysis.

Many studies have indicated possible associations between a polymorphism of adiponectin receptor 1 (ADIPOR1) rs1342387 and risk of cancer, but contradictory results have been reported. The main aim of this study was to draw a reliable conclusion about the relationship between the rs1342387 polymorphism and cancer incidence, by conducting a literature search of Pubmed, Embase, Wanfang and Cochrane libraries. Eleven studies including 3, 738 cases and 4, 748 controls were identified in this meta-analysis. The ADIPOR1 rs1342387 polymorphism was associated with risk of colorectal cancer for all genetic comparison models (GG vs AA, OR: 1.44, 95%CI: 1.21 -1.70; G carriers vs A carriers, OR: 1.23, 95%CI: 1.11 -1.36; dominant model, OR: 1.28, 95%CI: 1.10 -1.49 and recessive model, OR: 1.31, 95%CI: 1.12 -1.55). Stratified by ethnicity, the rs1342387 polymorphism was significantly associated with risk of colorectal cancer in Asian ancestry for all genetic comparison models (GG vs AA, OR: 1.56, 95%CI: 1.26-1.92; G carriers vs. A carriers OR: 1.30, 95%CI: 1.18 -1.43; dominant model OR: 1.31, 95%CI: 1.08 -1.60 and recessive model OR: 1.44, 95%CI: 1.26 -1.64), but not in Caucasian or mixed (Caucasian mainly) groups. In summary, the ADIPOR1 rs1342387 polymorphism is significantly associated with risk of colorectal cancer among individuals of Asian ancestry.

Meta-analysis of genome-wide association studies identifies novel loci that influence cupping and the glaucomatous process.

Glaucoma is characterized by irreversible optic nerve degeneration and is the most frequent cause of irreversible blindness worldwide. Here, the International Glaucoma Genetics Consortium conducts a meta-analysis of genome-wide association studies of vertical cup-disc ratio (VCDR), an important disease-related optic nerve parameter. In 21,094 individuals of European ancestry and 6,784 individuals of Asian ancestry, we identify 10 new loci associated with variation in VCDR. In a separate risk-score analysis of five case-control studies, Caucasians in the highest quintile have a 2.5-fold increased risk of primary open-angle glaucoma as compared with those in the lowest quintile. This study has more than doubled the known loci associated with optic disc cupping and will allow greater understanding of mechanisms involved in this common blinding condition.

Incidence of intracranial germ cell tumors by race in the United States, 1992-2010.

Little is known about the etiology of intracranial germ cell tumors (iGCTs), although international incidence data suggest that the highest incidence rates occur in Asian countries. In this analysis, we used 1992-2010 data from the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) Program to determine whether rates of iGCT were also high in Asian/Pacific Islanders living in the United States. Frequencies, incidence rates and survival rates were evaluated for the entire cohort and for demographic subgroups based on sex, age category (0-9 and 10-29 years), race (white, black, and Asian/Pacific Islander), and tumor location (pineal gland vs. other) as sample size permitted. Analyses were conducted using SEER*Stat 8.1.2. We observed a significantly higher incidence rate of iGCT in Asian/Pacific Islanders compared with whites (RR = 2.05, 95 % CI 1.57-2.64, RR = 3.04, 95 % CI 1.75-5.12 for males and females, respectively) in the 10-29 year age group. This difference was observed for tumors located both in the pineal gland and for tumors in other locations. Five-year relative survival differed by demographic and tumor characteristics, although these differences were not observed in comparisons limited to cases treated with radiation. Increased incidence rates of iGCT in individuals of Asian descent in the SEER registry are in agreement with data from the International Agency for Research on Cancer, where Japan and Singapore were among the countries with highest incidence. The increased incidence in individuals of Asian ancestry in the United States suggests that underlying genetic susceptibility may play a role in the etiology of iGCT.

A case of external auditory canal chondroma

The differential diagnosis for an external auditory canal mass is relatively broad, with exostosis, osteoma, fibroma, keratoma, and congenital cholesteatoma among the more common diagnoses. However, an additional diagnosis, external auditory canal chondroma, should also be considered in the differential. These rare lesions are most often found in individuals of Asian ancestry. However, this is not always the case as demonstrated by this case report of an external auditory canal chondroma in a Caucasian teenager.

Abstract 2291: Incidence of intracranial germ cell tumors by race in the United States, 1992-2009: A potential link with autoimmune encephalitis?.

Abstract Introduction: Pediatric germ cell tumors (GCTs) are rare and heterogeneous tumors that are grouped together due to their presumed common cell of origin, the primordial germ cell (PGC). GCTs typically occur in the testes or ovaries; however, abnormal prenatal PGC migration along with lack of apopotosis can result in tumors in extragonadal locations, including the central nervous system (intracranial and intraspinal GCTs; iGCTs). Little is known about the etiology of iGCTs, although international incidence data suggest that the highest incidence occurs in Asian countries. Autoimmune encephalitis (AE) is a paraneoplastic event characterized by abnormal behavior, seizures, and movement disorders; a number of case reports find AE in conjunction with GCT. We note with interest that a recent registry based study in California reported the highest incidence of AE in Asians. In this analysis, we used 1992-2009 data from the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) Program to determine whether the increased rates of iGCT observed in Asian countries was also seen in Asian/Pacific Islanders living in the United States. Methods: Frequencies and incidence rates were evaluated for the entire cohort and for demographic subgroups based on sex, age category (0-9 and 10-29 years), race (white, black, American Indian/Alaskan Native and Asian/Pacific Islander), and tumor location (pineal gland vs. other) as sample size permitted. Analyses were conducted using SEER*Stat 7.1.0. Results: Two peaks in incidence were observed, the first before age 1 year in both sexes and the second at age 10 years for females and age 18 years for males. We observed a significantly higher incidence rate of iGCT in Asian/Pacific Islanders compared with whites (RR=1.98, 95% CI 1.51-2.56 for males and RR=3.21, 95% CI 1.99-5.05 for females) in the 10-29 year age group. This difference was observed for tumors located both in the pineal gland and for tumors in other locations. Conclusions: The increased rates of iGCT we observed in individuals of Asian descent in the SEER registry are in agreement with data from the International Agency for Research on Cancer, where the highest incidence rates were observed in Japan, Singapore, and the Maori population of New Zealand. The explanation for these rate differences has not been investigated to date; however, the increased incidence in individuals of Asian ancestry in the United States suggests that genetic susceptibility may play a role in etiology. The higher frequency of AE in Asians and the co-occurrence with GCT in case reports is also intriguing. It is possible that AE could be triggered by PGCs abnormally present in the cranio-spatial axis prior to GCT diagnosis, and it will be of interest to determine whether a diagnosis of AE precedes iGCT. These differences in incidence patterns by race and the possible link with AE merit further investigation. Citation Format: Jenny N. Poynter, Rachel Fonstad, Jakub Tolar, Logan G. Spector, Julie A. Ross. Incidence of intracranial germ cell tumors by race in the United States, 1992-2009: A potential link with autoimmune encephalitis?. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2291. doi:10.1158/1538-7445.AM2013-2291

Frequency and function of CETP variants among individuals of Asian ancestry

Genetic variation in CETP (cholesteryl ester transfer protein) has been clearly associated with HDL cholesterol levels but its association with cardiovascular disease and related phenotypes has been more controversial, possibly due to variability of polymorphisms and their frequencies across different ethnic populations. To see if there are undetected polymorphisms affecting protein sequence in individuals of Asian ancestry and to determine the functionality of such variants, all exons and adjacent intronic segments were resequenced in 96 individuals and the observed variants cloned and analyzed. Two novel SNPs, including one coding change, S332 to Y332, were identified. Y332 and all other reported variants in Asians were cloned for study in vitro. Secretion efficiency was determined by Western blotting of protein from cell lysates and media. Cholesteryl ester transfer activity was measured in vitro by following the extent of transfer of fluorescently labeled substrate. Y332, Q296 and G442 are all secreted less well than wild type protein but retain significant transfer activity. P151 is not secreted and no transfer activity was detected. These protein variants should all contribute to higher HDL cholesterol in individuals carrying them. Additionally, a splicing variation that causes a protein truncation and non-functional CETP that has been reported predominantly in Asians was also found in two individuals of European ancestry and was on the same haplotype background in the two populations, suggesting a common origin of this null variant. This improved understanding of CETP variation in Asians will allow a more effective comparison of studies across populations.

A SNP in the ABCC11 gene is the determinant of human earwax type

Human earwax consists of wet and dry types. Dry earwax is frequent in East Asians, whereas wet earwax is common in other populations. Here we show that a SNP, 538G --> A (rs17822931), in the ABCC11 gene is responsible for determination of earwax type. The AA genotype corresponds to dry earwax, and GA and GG to wet type. A 27-bp deletion in ABCC11 exon 29 was also found in a few individuals of Asian ancestry. A functional assay demonstrated that cells with allele A show a lower excretory activity for cGMP than those with allele G. The allele A frequency shows a north-south and east-west downward geographical gradient; worldwide, it is highest in Chinese and Koreans, and a common dry-type haplotype is retained among various ethnic populations. These suggest that the allele A arose in northeast Asia and thereafter spread through the world. The 538G --> A SNP is the first example of DNA polymorphism determining a visible genetic trait.