Genetic variants in BMP8B gene are associated with growth traits in Chinese native cattle

As a signaling molecule, bone morphogenetic protein 8B (BMP8B) plays an essential role in bone metabolism and is able to regulate thermogenesis and energy balance, which suggests that BMP8B gene may be a new candidate for growth traits. Here, to characterize the effects of BMP8B gene on growth traits, we first used three Chinese indigenous cattle breeds (n = 845) to detect single nucleotide polymorphisms (SNPs). Five novel SNPs of BMP8B gene (g.− 242C>T, g.2164C>T, g.2639T>C, g.2900C>G and g.10817C>T) were identified by DNA pool sequencing and forced PCR–RFLP. And then we associated the five SNPs with four growth traits (body weight, body length, heart girth, and hucklebone width). Results from association analysis showed that the SNPs 1, 2, and 3 affected growth trait(s) markedly (P < 0.05). Further, 6 combined haplotypes were constructed to guarantee the reliability of analysis results. There were also significant differences in body length, heart girth and body weight between the 6 combined haplotypes (P < 0.05), but not in hucklebone width (P > 0.05). Collectively, our results suggest a modulatory role of BMP8B gene in cattle growth and development, and 3 SNPs could be used as molecular markers in early marker assisted selection (MAS) in beef cattle breeding program.     

Identification of bovine NPC1 gene cSNPs and their effects on body size traits of Qinchuan cattle

NPC1 gene is an important gene closely related to the Niemann–Pick type C (NPC). Mutations in the NPC1 gene tend to cause Niemann–Pick type C, a lysosomal storage disorder. Previous studies have shown that NPC1 protein plays an important role in subcellular lipid transport, homeostasis, platelet function and formation, which are basic metabolic activities in the process of development. In this study, to explore the association between the NPC1 gene variation and body size traits in Qinchuan cattle, we detected four novel coding single nucleotide polymorphisms (cSNPs) in the bovine NPC1 gene, including one missense mutation (SNP1) and three synonymous mutations (SNP2, SNP3 and SNP4). Population genetic analyses of 518 individuals and association correlations between cSNPs and bovine body size traits were conducted in this research. A missense mutation at SNP1 locus was found to be significantly related to the heart girth, hip width and body weight (P < 0.01 or P < 0.05, 3.5-year-old). Two synonymous mutations at SNP2 and SNP3 loci also showed significant effects on hip width (P < 0.05, 3.5-year-old). One synonymous mutation at SNP4 locus showed significant effect on body weight (P < 0.05, 2.0-year-old). Combined haplotypes H₂H₆ and H₆H₆ showed significant effects on body size traits such as heart girth, hip width, and body weight (3.5-year-old, P < 0.01 or P < 0.05). This study provides evidence that the NPC1 gene might be involved in the regulation of bovine growth and body development, and may be considered as a candidate gene for marker assisted selection (MAS) in beef cattle breeding industry.     

Haplotypes and effects on growth traits of bovine Wnt7a gene in Chinese Qinchuan cattle

Wnt7a is a member of the WNT gene family, which encodes secreted signaling proteins and responds to many biological processes. Specifically Wnt7a influences satellite stem cells and regulates the regenerative potential of the muscle. However, similar researches about the bovine Wnt7a gene are lacking. Therefore, in this study, polymorphisms of the bovine Wnt7a gene were detected in 488 individuals from Chinese Qinchuan cattle by DNA pooling, forced PCR-RFLP, and DNA sequencing methods. 3 novel SNPs were identified, two SNPs (g.T4926C and g.A21943G) were in the intron and the last one (g.C63777T) was in the exon. Five haplotypes involved in these three variant sites in the Wnt7a gene were identified and their effects on growth traits were analyzed. The results revealed that haplotype 1 had the highest haplotype frequencies and was highly significantly associated with body height (P < 0.01), body weight (P < 0.05), chest width (P < 0.05) and height at hip cross (P < 0.01) respectively.     

Assessment of association between variants and haplotypes of the IGF2 gene in beef cattle

Insulin-like growth factor 2 (IGF2) is a fetal growth and differentiation factor that plays an important role in muscle growth and in myoblast proliferation and differentiation. The aim of this study was to examine the association of the IGF2 polymorphism with growth traits in beef cattle breed. Four single nucleotide polymorphisms (SNPs: 1–4) were identified in the bovine IGF2 by sequencing pooled DNA samples (Pool-Seq) and forced polymerase chain reaction–restriction fragment length polymorphism (Forced PCR–RFLP) methods. The result of haplotype analysis of four SNPs showed that eight haplotypes and eighteen combined genotypes were revealed, and the linkage disequilibrium and evolutionary relationship were assessed in 1522 individuals representing four purebred cattle breeds from China. The statistical analyses indicated that the 4 SNPs and 18 combined genotypes or haplotypes are associated with the body weight at 18 and 24 months in Jiaxian cattle population (P < 0.05 or P < 0.01). Our results provide evidence that polymorphisms in the IGF2 gene are associated with growth traits, and may be used for marker-assisted selection in beef cattle breeding program.     

XRCC1 polymorphisms and differentiated thyroid carcinoma risk: A meta-analysis

The objective of this study is to quantitatively derive a more precise estimation of the association between X-ray repair cross-complementing group 1 (XRCC1) gene polymorphisms and differentiated thyroid carcinoma risk. A comprehensive literature search of three databases was conducted. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated with fixed-effect models and random-effect models when appropriate. Overall, no association of the XRCC1 Arg399Gln, Arg280His, and Arg194Trp polymorphisms with differentiated thyroid carcinoma risk was found. In subgroup analyses, a decreased differentiated thyroid carcinoma risk was observed among Caucasians (Gln vs. Arg, OR = 0.86, 95% CI = 0.77–0.96, P = 0.343 for heterogeneity; Gln/Arg vs. Arg/Arg, OR = 0.84, 95% CI = 0.71–0.98, P = 0.229 for heterogeneity; Gln/Gln vs. Arg/Arg, OR = 0.77, 95% CI = 0.60–0.99, P = 0.477 for heterogeneity; dominant genetic model, OR = 0.82, 95% CI = 0.71–0.95, P = 0.272 for heterogeneity), not among Asians. No publication bias was observed. Our results suggest that XRCC1 Arg399Gln polymorphism is not associated with differentiated thyroid carcinoma risk, while a decreased risk is observed among Caucasian population.     

Association between IL13 gene polymorphisms and susceptibility to cancer: A meta-analysis

Background/aims

Interleukin-13 (IL13) is an immunoregulatory cytokine which plays an important role in carcinogenesis through affecting tumor immunosurveillance. Many studies had reported the influence of IL13 rs1800925 and rs20541 polymorphisms on cancer risk, however, with inconclusive results. The aim of the present study was to conduct a meta-analysis to clarify the relationship.

Methods

Twenty studies including a total of 6713 cancer cases and 8693 controls for IL13 rs20541 polymorphism and 4081 cancer cases and 6202 controls for IL13 rs1800925 polymorphism were included in the meta-analysis. Data were extracted from these studies and odds ratios with corresponding 95% confidence intervals were computed to estimate the strength of the association.

Results

Overall, the IL13 rs20541 polymorphism were associated with significantly decreased cancer risk in all genetic models (AA vs. GG: OR = 0.82, 95%CI = 0.71–0.95; GA vs. GG: OR = 0.92, 95%CI = 0.85–0.99; GA/AA vs. GG: OR = 0.90, 95%CI = 0.85–0.97; AA vs. GG/GA: OR = 0.85, 95CI% = 0.74–0.98). In the stratified analyses, significant effects were found among European populations, studies with population-based controls and studies of glioma. No influence of the IL13 rs1800925 polymorphism on the overall cancer risk was observed. However, in the stratified analyses, we found the IL13 rs1800925 polymorphism was significantly associated with decreased risk for glioma (CT vs. TT: OR = 0.72, 95%CI = 0.55–0.93; CT/TT vs. TT: OR = 0.76, 95%CI = 0.62–0.89).

Conclusion

Our meta-analysis suggests that the IL13 rs20541 polymorphism contributes to susceptibility to cancer, especially for glioma; and the IL13 rs1800925 polymorphism may be associated with glioma risk.     

Calpain-10 genetic polymorphisms and polycystic ovary syndrome risk: A meta-analysis and meta-regression

Recent evidences suggest that common functional polymorphisms in the promoter region of the Calpain-10 gene may have an impact on an individual's susceptibility to polycystic ovary syndrome (PCOS), but individually published results are inconclusive. Our meta-analysis is aimed to provide a more precise estimation of the relationships between Calpain-10 genetic polymorphisms and PCOS risk. An extensive literature search for relevant studies was conducted on PubMed, Embase, Web of Science, Cochrane Library, and CBM databases from inception through April 1st, 2013. This meta-analysis was performed using the STATA 12.0 software. The crude odds ratio (OR) with 95% confidence interval (CI) was calculated. Fourteen case–control studies were included with a total of 2123 PCOS patients and 3612 healthy controls. Nine common SNPs in the Calpain-10 gene were addressed. Our meta-analysis indicated that UCSNP-19, UCSNP-63 and UCSNP-45 polymorphisms in the Calpain-10 gene might be associated with increased PCOS risk. However, no statistically significant association was observed in UCSNP-43, UCSNP-22, UCSNP-43, UCSNP-45, UCSNP-56, UCSNP-58, and UCSNP-110 polymorphisms. Further subgroup analysis by ethnicity revealed that UCSNP-19, UCSNP-63 and UCSNP-45 polymorphisms might decrease the risk of PCOS among Asian populations, but not among Caucasian populations. The current meta-analysis indicates that UCSNP-19, UCSNP-63 and UCSNP-45 polymorphisms in the Calpain-10 gene may be risk factors for PCOS, especially among Asian populations.     

Haplotype distribution in the GLI3 gene and their associations with growth traits in cattle

The glioma-associated oncogene family zinc finger 3 gene (GLI3) mediates in all vertebrates hedgehog (Hh) signaling that plays an essential role in the induction and patterning of numerous cell types during invertebrate and vertebrate development. In this study, a total of 6 single nucleotide polymorphisms (SNPs: 1–6) were identified by polymerase chain reaction–single stranded conformational polymorphism (PCR–SSCP) and DNA pool sequencing, including all 13 exons and 12 exon–intron boundaries within the bovine GLI3 gene. 16 haplotypes and 13 combined genotypes were revealed and the linkage disequilibrium was assessed in 708 individuals representing three main cattle breeds from China. The statistical analyses indicated that the SNP2, 3 and 4 are associated with the body weight at birth and 6 months in Nanyang cattle population (P < 0.05). No significant association was detected between 11 combined genotypes and body weight at five different ages. Our results provide evidence that polymorphisms in the GLI3 gene are associated with growth traits, and may be used for marker-assisted selection in beef cattle breeding program.     

Sequence analysis of the equine ACTN3 gene in Australian horse breeds

The sarcomeric α-actinins, encoded by the genes ACTN2 and ACTN3, are major structural components of the Z-line and have high sequence similarity. α-Actinin-2 is present in all skeletal muscle fibres, while α-actinin-3 has developed specialized expression in only type 2 (fast, glycolytic) fibres.     

Association of XRCC1 Arg399Gln polymorphism with bladder cancer susceptibility: A meta-analysis

Genetic variations in DNA repair genes are thought to modify DNA repair capacity and may to be related to cancer susceptibility. However, epidemiological study results have been inconsistent. In this meta-analysis, we assessed 24 case–control studies of association between the X-ray repair cross complementing group 1 (XRCC1) Arg399Gln polymorphism and bladder cancer susceptibility in the general population and in Asian and non-Asian subgroups. A moderately significant association with bladder cancer risk was found for AG vs GG (OR = 1.110, 95% CI = 1.018–1.210). No significant associations with bladder cancer risk were found for AA vs GG (OR = 0.942, 95% CI = 0.823–1.077), the dominant model AA/AG vs GG (OR = 1.075, 95% CI = 0.990–1.167) and the recessive model AA vs AG/GG(OR = 0.890, 95% CI = 0.788–1.005). In subgroup analysis, a moderately significant association was also found for AG vs GG (OR = 1.091, 95% CI = 1.008–1.180) in non-Asian subgroup. The analysis suggests that the XRCC1 Arg399Gln polymorphism might be a moderate risk factor for bladder cancer, especially in non-Asian population.     

Effect of genetic variations within the SH2B2 gene on the growth of Chinese cattle

As an adaptor protein, apart from potentiating Janus kinase 2 (JAK2) activation and promoting the insulin signaling pathway, Src homology 2 B 2 (SH2B2) indirectly takes part in the regulation of glucose uptake through the c-Cb1/CAP/TC10 pathway, which can in turn affect growth. In this study, we identified a 4 bp indel mutation and three single nucleotide polymorphisms (SNPs) within the SH2B2 gene in 959 individuals from five Chinese cattle breeds by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and sequencing. Based on the four variations, 12 haplotypes were identified. Additionally, there was a tendency that in every population pair-wise linkages increased progressively from V1–V2 to V3–V4. By association analysis, positive effects of genotypes CC and CT (snp1220 locus), DI (4 bp indel locus), and CC (snp21049 locus) on growth traits were obtained. Furthermore, when combined, individuals with the combination CCDITTCC showed the best performance at an early age. These results were suggestive of an association of snp1220, 4 bp indel and snp12049 with growth performance in Nanyang cattle, indicating possibly the candidate role of the SH2B2 gene in marker assisted selection in a beef cattle breeding program.     

The interleukin-4 − 589C/T polymorphism and the risk of asthma: A meta-analysis including 7345 cases and 7819 controls

Background

A number of studies assessed the association of − 589C/T polymorphism in the promoter region of interleukin-4 (IL-4) with asthma in different populations. However, the results were contradictory. A meta-analysis was conducted to investigate the association between polymorphism in the IL-4 and asthma susceptibility.

Methods

Databases including Pubmed, EMBASE, Wanfang Database, China National Knowledge Infrastructure (CNKI) and Weipu Database were searched to find relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations.

Results

Thirty-four studies involving 7345 cases and 7819 controls were included. Overall, significant association between − 589C/T polymorphism and asthma was observed for TT + CT vs. CC (OR = 1.26; 95% CI 1.12–1.42; P = 0.0001; I² = 26%). In the subgroup analysis by ethnicity, significant associations were found among Asians (OR = 1.36; 95% CI 1.07–1.73; P = 0.01; I² = 0%) and Caucasians (OR = 1.30; 95% CI 1.09–1.54; P = 0.004; I² = 53%) but not among African Americans (OR = 1.20; 95% CI 0.72–2.00; P = 0.48; I² = 48%). In the subgroup analysis by atopic status, no significant association was found among atopic asthma patients (OR = 1.20; 95% CI 0.92–1.34; P = 0.27; I² = 6%) and non-atopic asthma patients (OR = 0.97; 95% CI 0.73–1.28; P = 0.81; I² = 0%).

Conclusions

This meta-analysis suggested that the IL-4 − 589C/T polymorphism was a risk factor of asthma.     

Distribution of GSTM1, GSTT1, GSTP1 and TP53 disease-associated gene variants in native and urban Venezuelan populations

The contemporary Venezuelan population is the product of major admixture process across various historical events, which has provided it a particular genetic background. The aim of this study concerns the analysis of glutathione S-transferase (GST) GSTM1, GSTP1 and GSTT1 genetic variants and five polymorphisms at the TP53 gene, which are related to cancer susceptibility, in an urban/admixed population and five Amerindian tribes (Bari, Panare, Pemon, Warao and Wayuu) from Venezuela. Genotyping was carried out in 120 individuals from an urban sample and 188 Amerindians. The analysis performed on TP53 haplotype and GST allele distribution showed a close correlation for Pemon and Warao populations, while Bari group appears isolated from the other populations. GSTT1 null variant frequency in our admixed (11%) and native samples (0.0–11.4%) was lower when compared with Caucasians, Africans and Asians. Frequency of the GSTP1*Val cancer-associated allele found in Bari (88.6%) and Panare (63.0%) is of the highest so far reported. Fourteen TP53 haplotypes were observed in the admixed populations, whereas only 3 to 5 in Amerindians. To our knowledge this is the first report of GST polymorphisms and TP53 haplotype distribution in Venezuelans. The distribution of most of analyzed polymorphisms in the urban sample is consistent with the admixed origin of the present-day population of Venezuela. While, the inter-ethnic variations in genetic polymorphisms found in Native American tribes seem to be the result of the influence of demographic factors. These results provide additional data for undertaking ethnographic and disease association studies in Venezuela.     

Polymorphisms of the TLR4 gene and risk of gastric cancer

Objective

Toll-like receptor 4 (TLR4) is an important lipo-polysaccharide (LPS) receptor in gastric epithelial cell signaling transduction and plays critical roles in the development and progression of gastric cancer (GC). We investigated the effects of TLR4 gene polymorphisms and gene–environmental interactions on the risk of GC in Northeastern China.

Methods

We genotyped two single-nucleotide polymorphisms (SNPs) in TLR4 (rs10116253 and rs1927911) in 217 GC patients and 294 cancer-free controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Odds ratio (OR) and 95% confidence intervals (CIs) were estimated by unconditional logistic-regression models.

Results

Individuals carrying CC genotype of rs10116253 and TT genotype of rs1927911 had a significantly decreased risk of GC (adjusted OR = 0.33, 95% CI 0.18–0.60, P < 0.001 and adjusted OR = 0.37, 95% CI 0.21–0.67, P = 0.001 respectively), compared with TT genotype of rs10116253 and CC genotype of rs1927911. In addition, the SNP effects were additive to the effects of some known environmental factors without any interaction between them in the susceptibility to GC.

Conclusion

Our data suggested that TLR4 gene polymorphisms may be associated with a decreased risk of GC in Chinese population. And these SNPs and their combined effects with environmental factors may be associated with the risk of GC.     

The XRCC1 Arg280His polymorphism contributes to cancer susceptibility: an update by meta-analysis of 53 individual studies

The X-ray repair cross-complementing group 1 (XRCC1) protein plays a central role in DNA repair pathways. Epidemiological studies have revealed the association between XRCC1 Arg280His polymorphism and cancer risk, but the results were inconsistent. We conducted this meta-analysis to assess the effect of XRCC1 Arg280His polymorphism on cancer susceptibility with accumulated data. Up to January 2012, 53 case‐control studies with 21,349 cases and 23,649 controls were available for our study. Summary odds ratios (OR) and corresponding 95% confidence intervals (CIs) for XRCC1 Arg280His polymorphism and cancer were estimated using fixed‐ or random-effects models when appropriate. Our meta-analysis identified that elevated cancer risk was statistically associated with the minor variant His allele and Arg–His/His–His genotypes both in the overall population (allele comparison, His versus Arg: OR = 1.16; 95% CI: 1.08–1.25; dominant comparison, Arg–His/His–His versus Arg–Arg: OR = 1.17; 95% CI: 1.08–1.27) and in terms of subgroup analyses by ethnicity for both Caucasians and non‐Caucasians. However, no significant result was observed in the stratified analysis by cancer type. Moreover, significantly increased cancer risk was observed in smokers. These findings indicated that XRCC1 Arg280His polymorphism may play a role in cancer development.