Beta-2-microglobulin haplotypes in U.S. beef cattle and association with failure of passive transfer in newborn calves

Failure of passive transfer (FPT) is a condition in which neonates do not acquire protective serum levels of maternal antibodies. A principal component of antibody transport is the neonatal receptor for the Fc portion of immunoglobulin, a heterodimer of a MHC-1 alpha-chain homolog (FCGRT) and beta-2-microglobulin (B2M). Previously, two FCGRT haplotypes were associated with differences in immunoglobulin G (IgG) passive transfer in cattle (Laegreid et al. (2002) Mamm Genome 13, 704–710). The present study had two objectives: first, to characterize the B2M haplotype structure in a diverse group of U.S. beef cattle, and second, to evaluate those haplotypes for association with either high or low serum IgG levels in newborn calves. Twelve single nucleotide polymorphisms (SNPs), assorted into eight haplotypes, were identified by sequencing regions of B2M exons II and IV in a multi-breed panel of 96 beef cattle. Calves homozygous for one of the eight haplotypes (B2M 2,2) were at increased risk of FPT (odds ratio = 10.60, CI_95% 2.07–54.24, p = 0.005). These results indicate that this haplotype is in linkage disequilibrium with genetic risk factors affecting passive transfer of IgG in beef calves, an important determinant of neonatal calf morbidity and mortality.     

Polymorphisms in DNA repair genes and risk of non-Hodgkin lymphoma among women in Connecticut

Several hereditary syndromes characterized by defective DNA repair are associated with high risk of non-Hodgkin lymphoma (NHL). To explore whether common polymorphisms in DNA repair genes affect risk of NHL in the general population, we evaluated the association between single nucleotide polymorphisms (SNPs) in DNA repair genes and risk of NHL in a population-based case–control study among women in Connecticut. A total of 518 NHL cases and 597 controls recruited into the study provided a biologic sample. Thirty-two SNPs in 18 genes involved in several DNA repair pathways were genotyped. Genotype data were analyzed by unconditional logistic regression adjusting for age and race. SNPs in four genes (ERCC5, ERCC2, WRN, and BRCA1) were associated with altered risk of NHL and diffuse large B-cell lymphoma (DLBCL), the major B cell subtype. In particular, ERCC5 Asp1104His was associated with increased risk of NHL overall (OR: 1.46; 95% CI: 1.13–1.88; P = 0.004), DLBCL (OR: 1.44; 95% CI: 0.99–2.09; P = 0.058), and also T cell lymphoma. WRN Cys1367Arg was associated with decreased risk of NHL overall (OR: 0.71; 95% CI: 0.56–0.91; P = 0.007) and DLBCL (OR: 0.66; 95% CI: 0.45–0.95; P = 0.024), as well as follicular and marginal zone lymphomas. Genetic polymorphisms in DNA repair genes, particularly ERCC5 and WRN, may play a role in the pathogenesis of NHL, especially for DLBCL. Further work is needed to extend these findings by carrying out extended haplotype analyses of these and related genes and to replicate the observations in other studies.     

Association of chromosome 8q24 variants with prostate cancer risk in the Siberian region of Russia and meta-analysis

Compelling evidence demonstrates chromosome 8q24 as a prostate cancer susceptibility locus. In present work we studied whether the common variants of 8q24 region, rs6983267 and rs1447295, were associated with the sporadic prostate cancer risk in the Russian population. Polymorphisms were genotyped in 393 case and 384 control Russian Caucasian men from Siberia region. The A allele of rs1447295 was significantly associated with the risk of prostate cancer (OR[CI 95%] = 1.74 [1.26-2.4], p = 7.8 x 10(-4)). A common G-A haplotype for rs6983267 - rs1447295 also showed an association with prostate cancer risk in Russian population (OR[CI 95%] = 2.03 [1.1 - 3.75], p = 0.02). We performed a meta-analysis combining our results with previous studies to evaluate the association between studied SNPs and prostate cancer risk. Meta-analysis has strongly supported the association for these SNPs (p < 10(-6)). Accordingly our study confirms the association between chromosome 8q24 and prostate cancer risk.     

The EPAS1 gene influences the aerobic–anaerobic contribution in elite endurance athletes

Absract EPAS1 is a gene involved in complex oxygen sensing. It is expressed in microvascular endothelial cells, lung epithelial cells, cardiac myocytes and the brain. An association study was undertaken comparing elite endurance athletes classified into two groups according to a power–time model of performance intensity: power–time-maximum (PT-MAX; N=242, event duration 50 s to 10 min) and power–time–steady state (PT-SS; N=151, event duration ~2–10 h), with normal controls (N=444) using 12 SNPs across EPAS1. Ordinal regression analysis of allele frequencies revealed significant differences at SNPs 2 and 3 (P=0.01). Haplotype analysis revealed the presence of haplotypes involving SNPs 2–5 that significantly differentiated (P<0.05) the groups based on an ordinal ranking using the power–time classification. These same haplotypes differentiated the PT-MAX group in which a significant decrease in a haplotype (F: G-C-C-G; OR=0.57, P=0.02, 95% CI 0.36–0.92) and increase in a second haplotype (G: A-T-G-G; OR=1.75, P=0.03, 95% CI 1.05–2.91) was observed compared to controls. The PT-SS group was differentiated from the PT-MAX group by a third haplotype (H: A-T-G-A; OR=0.46, P=0.04, 95% CI 0.22–0.96). Since EPAS1 has a role as a sensor capable of integrating cardiovascular function, energetic demand, muscle activity and oxygen availability into physiological adaptation, we propose that DNA variants in EPAS1 influence the relative contribution of aerobic and anaerobic metabolism and hence the maximum sustainable metabolic power for a given event duration.     

Genetic polymorphisms in transforming growth factor beta-1 (TGFB1) and childhood asthma and atopy

Transforming growth factor beta-1 (TGFB1) may influence asthma by modulating allergic airway inflammation and airway remodeling. The role of single nucleotide polymorphisms (SNPs) of TGFB1 in asthma remains inconclusive. We examined TGFB1 SNPs in relation to asthma risk and degree of atopy among 546 case-parent triads, consisting of asthmatics aged 4–17 years and their parents in Mexico City. Atopy to 24 aeroallergens was determined by skin prick tests. We genotyped five TGFB1 SNPs, including two known functional SNPs [C-509T (rs1800469), T869C (rs1982073)] and three others (rs7258445, rs1800472, rs8179181), using TaqMan and Masscode assays. We analyzed the data using log-linear and polytomous logistic methods. Three associated SNPs, including the two known functional SNPs, were statistically significantly related to asthma risk. Individuals carrying the T allele of C-509T had an increased risk of asthma [relative risk (RR) = 1.42, 95% confidence interval (CI) = 1.08–1.87 for one copy; RR (95%CI) = 1.95 (1.36–2.78) for two copies]. For T869C, the RRs (95%CI) were 1.47 (1.09–1.98) for one and 2.00 (1.38–2.90) for two copies of the C allele. Similar results were found for rs7258445. The haplotype containing all three risk alleles conferred an increased risk of asthma (RR = 1.48, 95% CI = 1.11–1.95 for one copy; RR = 1.77, 95% CI = 1.22–2.57 for two copies). These three SNPs were also related to the degree of atopy. This largest study to date of genetic variation in TGFB1 and asthma and atopy adds to increasing evidence for a role in these disorders.     

Vitamin D receptor gene polymorphisms and susceptibility of hand osteoarthritis in Finnish women

We examined whether polymorphisms of the vitamin D receptor (VDR) gene was associated with individual risk of hand osteoarthritis (OA). Radiographs of both hands of 295 dentists and of 248 teachers were examined and classified for the presence of OA using reference images. The VDR ApaI and TaqI genotypes were determined by PCR-based methods. No association was observed between the VDR polymorphisms and the odds of overall hand OA. However, the carriers of the VDR t allele or At haplotype were at almost half the odds of symmetrical hand OA (odds ratio [OR] = 0.60, 95% confidence interval [CI] = 0.38–0.94 and OR = 0.59, 95% CI = 0.38–0.93, respectively) compared with the carriers of the T allele and of the non-At haplotype, respectively. Increased odds of this disease, on the contrary, was observed for women with two copies of the VDR a allele (OR = 1.93, 95% CI = 1.99–3.70) compared with women with the AA genotype. Conversely, the VDR a allele carriage was associated with a tendency of lowered odds of osteophyte (OR = 0.51, 95% CI = 0.25–1.03). When the genotype data were used to construct haplotypes, the VDR AaTt joint genotype appeared to pose a remarkably lower odds (OR = 0.26, 95% CI = 0.08–0.91) of osteophyte compared with the AAtt joint genotype. As a novel finding we observed a joint effect of a low calcium intake and VDR polymorphisms on symmetrical OA; the OR was 2.64 (95% CI = 1.29–5.40) for carriers of the aT haplotype with low daily calcium intake compared with non-carriers of the haplotype with high daily calcium intake. Our results suggest that VDR gene polymorphisms play a role in the etiology of symmetrical hand OA. Moreover, the association between the VDR gene and OA may be modified by calcium intake.     

Association of CTLA-4 gene polymorphisms with sporadic breast cancer risk and clinical features in Han women of Northeast China

Cytotoxic T lymphocyte antigen-4 (CTLA-4) is an inhibitory molecule that plays a pivotal role in downregulating T-cell mediated immune responses. To determine the role of CTLA-4 in tumor immunity, and to validate previous results as well, we investigated four tag single nucleotide polymorphisms (SNPs) of CTLA-4 in a relatively large Chinese Han cohort from northeastern China. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 581 patients and 566 age-matched controls. Our data indicated that compared with the common genotype and allele of each SNP, the -1722 CC genotype and C allele showed an increased risk of breast cancer (P = 0.030, odds ratio (OR) = 1.457, 95% confidence internal (CI) 1.036-2.051; P = 0.024, OR = 1.214, 95% CI 1.026-1.436, respectively). The -1661 GG genotype and G allele were also associated with an increased risk of breast cancer (P = 0.018, OR = 1.396, 95% CI 1.058-1.843; P = 0.013, OR = 1.353, 95% CI 1.066-1.717, respectively). In the haplotype analysis, the CAAA haplotype showed a higher frequency in cases (P = 0.004), and this association remained significant after correcting the P value for multiple testing. Associations were shown between the SNPs of CTLA-4 and lymph node metastasis, estrogen receptor (ER), progesterone receptor (PR) and P53 statuses. These results indicate that some SNPs in the CTLA-4 gene may affect the risk of breast cancer and show that some SNPs are associated with breast cancer characteristics in Han women in northeastern China.     

Association of polymorphisms of endothelial nitric oxide synthase (eNOS) gene with the risk of primary open angle glaucoma in a Brazilian population

The present study aimed to investigate the association of endothelial nitric oxide synthase (eNOS) gene polymorphisms with primary open angle glaucoma (POAG). We conducted a case-control study that included 90 patients with POAG and 127 healthy controls whose blood samples were genotyped for the functional polymorphisms T-786C and Glu298Asp of the eNOS gene by Taqman fluorescent allelic discrimination assay. The T-786C polymorphism was significantly associated as a risk factor for POAG among women (OR: 2.28; 95% CI: 1.11 to 4.70, p=0.024) and marginally associated to the risk of POAG in the patients ≥52 years of age at diagnosis (OR: 2.11; 95% CI: 0.98 to 4.55, p=0,055). However, these results was not confirmed after adjustments for gender, age, self-declared skin color, tobacco smoking and eNOS genotypes by multivariate logistic regression model (OR: 2.08; 95% CI: 0.87 to 5.01, p=0.101 and OR: 2.20; 95% CI: 0.95 to 5.12, p=0.067, respectively). The haplotype CG of T-786C and Glu298Asp showed a borderline association with risk of POAG in the overall analysis (OR: 1.76; 95% CI: 0.98 to 3.14, p=0.055) and among women (OR: 2.02; 95% CI: 0.98 to 4.16, p=0.052). Furthermore, the CG haplotype was significantly associated with the development of POAG for the age at diagnosis group ≥52 years (OR: 3.48; 95% CI: 1.54 to 7.84, p=0.002).We suggested that haplotypes of the polymorphisms T-786C and Glu298Asp of eNOS may interact with gender and age in modulating the risk of POAG.     

Polymorphisms in the AKT1 and AKT2 genes and oesophageal squamous cell carcinoma risk in an Eastern Chinese population

Ethnic Han Chinese are at high risk of developing oesophageal squamous cell carcinoma (ESCC). Aberrant activation of the AKT signalling pathway is involved in many cancers, including ESCC. Some single nucleotide polymorphisms (SNPs) in genes involved in this pathway may contribute to ESCC susceptibility. We selected five potentially functional SNPs in AKT1 (rs2494750, rs2494752 and rs10138277) and AKT2 (rs7254617 and rs2304186) genes and investigated their associations with ESCC risk in 1117 ESCC cases and 1096 controls in an Eastern Chinese population. None of individual SNPs exhibited an association with ESCC risk. However, the combined analysis of three AKT1 SNPs suggested that individuals carrying one of AKT1 variant genotypes had a decreased ESCC risk [adjusted odds ratio (OR) = 0.60, 95% CI = 0.42–0.87]. Further stratified analysis found that AKT1 rs2294750 SNP was associated with significantly decreased ESCC risk among women (adjusted OR = 0.63, 95% CI = 0.43–0.94) and non‐drinkers (OR = 0.79, 95% CI = 0.64–0.99). Similar protective effects on women (adjusted OR = 0.56, 95% CI = 0.37–0.83) and non‐drinker (adjusted OR = 0.75, 95% CI = 0.60–0.94) were also observed for the combined genotypes of AKT1 SNPs. Consistently, logistic regression analysis indicated significant gene–gene interactions among three AKT1 SNPs (P < 0.015). A three‐AKT1 SNP haplotype (C‐A‐C) showed a significant association with a decreased ESCC risk (adjusted OR = 0.70, 95% CI = 0.52–0.94). Multifactor dimensionality reduction analysis confirmed a high‐order gene–environment interaction in ESCC risk. Overall, we found that three AKT1 SNPs might confer protection against ESCC risk; nevertheless, these effects may be dependent on other risk factors. Our results provided evidence of important gene–environment interplay in ESCC carcinogenesis.     

Polymorphisms in the pituitary growth hormone gene and its receptor associated with coronary artery disease in a predisposed cohort from India

We investigated the promoter polymorphisms of the pituitary growth hormone gene (GH1) and exon 3 deletion polymorphism (GHRd3) in its receptor gene (GHR) in 299 angiographically proven patients with coronary artery disease (CAD) and 231 asymptomatic controls enrolled in the ongoing Indian Atherosclerosis Research Study. Real time PCR based analysis of the GHR variant showed significant association of the GHRd3 deletion allele with CAD (OR 0.48, 95% CI: 0.30–0.76, P = 0.0014) and a dominant model of inheritance (Akaike information criterion = 482). The deletion allele showed significant association with high plasma HDL-c levels (P = 0.001). Sequencing of the proximal promoter region of GH1 revealed 12 novel polymorphisms and a TAGA haplotype constituted by the functional SNPs rs2005171, rs11568828, rs2005172 and rs6171, that showed significant association with CAD alone (adjusted OR of 3.31 (95% CI = 1.33–8.29, P = 0.011) and in CAD patients with diabetes (P = 0.019). Mean standardized height was associated with three of the four haplotype-tagging SNPs in the cohort (P ≤ 0.03). Eleven of the 12 polymorphic promoter SNPs contributed to 14.7% of variation in height in females in the whole dataset (P = 0.029). CAD patients with history of stroke exhibited marginally significantly lower mean height as compared to rest of the cohort (P < 0.006). In conclusion, genetic polymorphisms in the GHR gene and its ligand, GH1, may modulate the risk of CAD in the Asian Indian population.     

Haplotypes in the promoter region of the ADIPOQ gene are associated with increased diabetes risk in a German Caucasian population.

Adiponectin, which is encoded by the ADIPOQ gene, has been shown to modulate insulin sensitivity and glucose homeostasis. Plasma adiponectin levels are decreased in type 2 diabetes and obesity. Genetic variations within the ADIPOQ gene are associated with decreased adiponectin hormone levels. To analyze specific single-nucleotide polymorphisms (SNPs) and their association with T2D, 365 German subjects with T2D and 323 control subjects were screened. Three common SNPs - +45T>G in exon 2, and 2 promoter variants SNPs -11391G>A and -11377C>G - were analyzed. We found that the variant allele of SNP -11391G>A was significantly more frequent in the diabetic patient group than in the control group (p=0.003). Carrying the haplotype of SNP -11391A and SNP -11377C was associated with a 1.50-fold (p=0.03) increase in diabetes risk. The combination of the A-C haplotype and the G-C haplotype was associated with significantly elevated diabetes risk (OR=2.82 (95% CI: 1.35-5.91), p=0.006) after correction for BMI and age. Our observations suggest that diploid combinations of haplotype in the adiponectin gene promoter region contribute to the genetic risk of T2D in individuals from a German Caucasian population.     

EphB2 SNPs and sporadic prostate cancer risk in African American men

The EphB2 gene has been implicated as a tumor suppressor gene somatically altered in both prostate cancer (PC) and colorectal cancer. We have previously shown an association between an EphB2 germline nonsense variant and risk of familial prostate cancer among African American Men (AAM). Here we set out to test the hypothesis that common variation within the EphB2 locus is associated with increased risk of sporadic PC in AAM. We genotyped a set of 341 single nucleotide polymorphisms (SNPs) encompassing the EphB2 locus, including known and novel coding and noncoding variants, in 490 AA sporadic PC cases and 567 matched controls. Single marker-based logistical regression analyses revealed seven EphB2 SNPs showing statistically significant association with prostate cancer risk in our population. The most significant association was achieved for a novel synonymous coding SNP, TGen-624, (Odds Ratio (OR) =?0.22; 95% Confidence Interval (CI) 0.08-0.66, p?=?1×10(-5)). Two other SNPs also show significant associations toward a protective effect rs10465543 and rs12090415 (p?=?1×10(-4)), OR?=?0.49 and 0.7, respectively. Two additional SNPs revealed trends towards an increase in risk of prostate cancer, rs4612601 and rs4263970 (p?=?0.001), OR?=?1.35 and 1.31, respectively. Furthermore, haplotype analysis revealed low levels of linkage disequilibrium within the region, with two blocks being associated with prostate cancer risk among our population. These data suggest that genetic variation at the EphB2 locus may increase risk of sporadic PC among AAM.     

Association of chromosome 8q24 variants with prostate cancer risk in the Siberian region of Russia and meta-analysis

Compelling evidence demonstrates the importance of chromosome 8q24 as a locus of susceptibility to prostate cancer. In this work, the association of common 8q24 variants, rs6983267 and rs1447295, with a sporadic risk of prostate cancer was analyzed in the Russian population of Siberia. For this purpose, the above polymorphisms were genotyped in 393 cases and 384 control individuals. The A allele of rs1447295 was significantly associated with prostate cancer risk (OR[CI 95%] = 1.74 [1.26–2.4], p = 7.8 × 10⁻⁴). The common G-A haplotype of rs6983267-rs1447295 also showed association with prostate cancer risk in Russians (OR[CI 95%] = 2.03 [1.1–3.75], p = 0.02). A meta-analysis combining our data with previously published results was performed to better evaluate the association between the SNPs studied and prostate cancer risk; its results strongly supported the association for both loci (p < 10⁻⁶). Thus, our study has confirmed the association of chromosome 8q24 with a risk of prostate cancer.     

Polymorphism of vascular endothelial growth factor −1154G>A (rs1570360) with cancer risk: a meta-analysis of 16 case–control studies

Published data on the association of vascular endothelial growth factor (VEGF) −1154G>A polymorphism with cancer risk is inconclusive. To derive a more precise estimation of association between VEGF −1154G>A polymorphism and the risk of cancer, we performed a meta-analysis of 7,071 cancer cases and 7,693 controls from 16 published case–control studies. Our meta-analysis didn’t reveal an association between VEGF −1154G>A polymorphism and overall cancer risk (GG vs. AA: OR: 1.08, 95% CI: 0.96–1.20; GA vs. AA: OR: 1.04, 95% CI: 0.93–1.17; recessive model: GG+GA vs. AA: OR: 1.06, 95% CI: 0.95–1.18; dominant model: GG vs. GA+AA, OR: 1.11, 95% CI: 1.00–1.24). Nevertheless, for non-Caucasians, GG homozygote may have higher cancer risk compared with either A carriers (OR: 1.58, 95% CI: 1.12–2.23) or AA homozygote (OR: 1.43, 95% CI: 1.17–1.76). No significant heterogeneity was detected except in the dominant model and “prostate cancer” subgroup analysis. More studies with larger samples are warranted to confirm these findings.     

Tumour necrosis factor -308 and -238 promoter polymorphisms are predictors of a null virological response in the treatment of Brazilian hepatitis C patients

Certain host single nucleotide polymorphisms (SNPs) affect the likelihood of a sustained virological response (SVR) to treatment in subjects infected with hepatitis C virus (HCV). SNPs in the promoters of interleukin (IL)-10 (-1082 A/G, rs1800896), myxovirus resistance protein 1 (-123 C/A, rs17000900 and -88 G/T, rs2071430) and tumour necrosis factor (TNF) (-308 G/A, rs1800629 and -238 G/A, rs361525) genes and the outcome of PEGylated α-interferon plus ribavirin therapy were investigated. This analysis was performed in 114 Brazilian, HCV genotype 1-infected patients who had a SVR and in 85 non-responders and 64 relapsers. A significantly increased risk of having a null virological response was observed in patients carrying at least one A allele at positions -308 [odds ratios (OR) = 2.58, 95% confidence intervals (CI) = 1.44-4.63, p = 0.001] or -238 (OR = 7.33, 95% CI = 3.59-14.93, p < 0.001) in the TNF promoter. The risk of relapsing was also elevated (-308: OR = 2.87, 95% CI = 1.51-5.44, p = 0.001; -238: OR = 4.20, 95% CI = 1.93-9.10, p < 0.001). Multiple logistic regression of TNF diplotypes showed that patients with at least two copies of the A allele had an even higher risk of having a null virological response (OR = 16.43, 95% CI = 5.70-47.34, p < 0.001) or relapsing (OR = 6.71, 95% CI = 2.18-20.66, p = 0.001). No statistically significant association was found between the other SNPs under study and anti-HCV therapy response.     

SNP Association Mapping across the Extended Major Histocompatibility Complex and Risk of B-Cell Precursor Acute Lymphoblastic Leukemia in Children

The extended major histocompatibility complex (xMHC) is the most gene-dense region of the genome and harbors a disproportionately large number of genes involved in immune function. The postulated role of infection in the causation of childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL) suggests that the xMHC may make an important contribution to the risk of this disease. We conducted association mapping across an approximately 4 megabase region of the xMHC using a validated panel of single nucleotide polymorphisms (SNPs) in childhood BCP-ALL cases (n=567) enrolled in the Northern California Childhood Leukemia Study (NCCLS) compared with population controls (n=892). Logistic regression analyses of 1,145 SNPs, adjusted for age, sex, and Hispanic ethnicity indicated potential associations between several SNPs and childhood BCP-ALL. After accounting for multiple comparisons, one of these included a statistically significant increased risk associated with rs9296068 (OR=1.40, 95% CI=1.19-1.66, corrected p=0.036), located in proximity to HLA-DOA. Sliding window haplotype analysis identified an additional locus located in the extended class I region in proximity to TRIM27 tagged by a haplotype comprising rs1237485, rs3118361, and rs2032502 (corrected global p=0.046). Our findings suggest that susceptibility to childhood BCP-ALL is influenced by genetic variation within the xMHC and indicate at least two important regions for future evaluation.     

Association between the European GWAS-Identified Susceptibility Locus at Chromosome 4p16 and the Risk of Atrial Septal Defect: A Case-Control Study in Southwest China and a Meta-Analysis

Atrial septal defect (ASD) is the third most frequent type of congenital heart anomaly, featuring shunting of blood between the two atria. Gene-environment interaction remains to be an acknowledged cause for ASD occurrence. A recent European genome-wide association study (GWAS) of congenital heart disease (CHD) identified 3 susceptibility SNPs at chromosome 4p16 associated with ASD: rs870142, rs16835979 and rs6824295. A Chinese-GWAS of CHD conducted in the corresponding period did not reveal the 3 susceptibility SNPs, but reported 2 different risk SNPs: rs2474937 and rs1531070. Therefore, we aimed to investigate the associations between the 3 European GWAS-identified susceptibility SNPs and ASD risk in the Han population in southwest China. Additionally, to increase the robustness of our current analysis, we conducted a meta-analysis combining published studies and our current case-control study. We performed association, linkage disequilibrium, and haplotype analysis among the 3 SNPs in 190 ASD cases and 225 age-, sex-, and ethnicity-matched healthy controls. Genotype and allele frequencies among the 3 SNPs showed statistically significant differences between the cases and controls. Our study found that individuals carrying the allele T of rs870142, the allele A of rs16835979, and the allele T of rs6824295 had a respective 50.1% (odds ratio (OR) = 1.501, 95% confidence interval (CI) = 1.122-2.009, P_FDR-BH = 0.018), 48.5% (OR = 1.485, 95%CI = 1.109-1.987, P_FDR-BH = 0.012), and 38.6% (OR = 1.386, 95%CI = 1.042-1.844, P_FDR-BH = 0.025) increased risk to develop ASD than wild-type allele carriers in our study cohort. In the haplotype analysis, we identified a disease-risk haplotype (TAT) (OR = 1.540, 95%CI = 1.030-2.380, P_FDR-BH = 0.016). Our meta-analysis also showed that the investigated SNP was associated with ASD risk (combined OR (95%CI) = 1.35 (1.24-1.46), P < 0.00001). Our study provides compelling evidence to motivate better understanding of the etiology of ASD.     

ICAM gene cluster SNPs and prostate cancer risk in African Americans

Intercellular adhesion molecules (ICAMs) are known to be involved in various human cancers. An ICAM gene cluster lying within a 26 kb region on chromosome 19p13.2, and containing ICAM1, ICAM4, and ICAM5 has recently been identified as harboring a breast and prostate cancer susceptibility locus in two populations of European ancestry from Germany and Australia. The objective of this study was to confirm the ICAM association with prostate cancer in a sample of African American prostate cancer cases (N = 286) and controls (N = 391). Six single nucleotide polymorphisms (SNPs) within the three ICAM genes were genotyped. To control for potential population stratification an ancestry-adjusted association analysis was performed. We found that ICAM1 SNPs, −9A/C (rs5490) and K469E (rs5498) were associated with prostate cancer risk in men with a family history of prostate cancer (P = 0.008). Specifically, increased risk was observed for individuals who possessed the CC genotype of the −9 A/C variant (odds ratio = 2.5; 95% CI = 1.0–6.3) and at least one G allele of non-synonymous K469E variant (odds ratio = 1.8; 95% CI = 1.2–3.1). Strong linkage disequilibrium was observed across the ICAM region (P < 0.001). A common haplotype within the ICAM gene cluster, harboring the −9A/C variant was significantly associated with prostate cancer (P = 0.03), mainly due to men with family history (P = 0.01). Our results replicate previous findings of association of the ICAM gene cluster with prostate cancer and suggest that common genetic variation within ICAM1 and not ICAM5 may be an important risk factor for prostate cancer.