Risk Alleles for Multiple Myeloma Susceptibility in ADME Genes

The cause of multiple myeloma (MM) remains largely unknown. Several pieces of evidence support the involvement of genetic and multiple environmental factors (i.e., chemical agents) in MM onset. The inter-individual variability in the bioactivation, detoxification, and clearance of chemical carcinogens such as asbestos, benzene, and pesticides might increase the MM risk. This inter-individual variability can be explained by the presence of polymorphic variants in absorption, distribution, metabolism, and excretion (ADME) genes. Despite the high relevance of this issue, few studies have focused on the inter-individual variability in ADME genes in MM risk. To identify new MM susceptibility loci, we performed an extended candidate gene approach by comparing high-throughput genotyping data of 1936 markers in 231 ADME genes on 64 MM patients and 59 controls from the CEU population. Differences in genotype and allele frequencies were validated using an internal control group of 35 non-cancer samples from the same geographic area as the patient group. We detected an association between MM risk and ADH1B rs1229984 (OR = 3.78; 95% CI, 1.18–12.13; p = 0.0282), PPARD rs6937483 (OR = 3.27; 95% CI, 1.01–10.56; p = 0.0479), SLC28A1 rs8187737 (OR = 11.33; 95% CI, 1.43–89.59; p = 0.005), SLC28A2 rs1060896 (OR = 6.58; 95% CI, 1.42–30.43; p = 0.0072), SLC29A1 rs8187630 (OR = 3.27; 95% CI, 1.01–10.56; p = 0.0479), and ALDH3A2 rs72547554 (OR = 2.46; 95% CI, 0.64–9.40; p = 0.0293). The prognostic value of these genes in MM was investigated in two public datasets showing that shorter overall survival was associated with low expression of ADH1B and SLC28A1. In conclusion, our proof-of-concept findings provide novel insights into the genetic bases of MM susceptibility.

Polymorphism of Insulin-induced gene 1 (INSIG1) of three local beef cattle in Indonesia

Insulin-induced gene 1 (INSIG1) encoded protein that blocked of proteolysis activity from protein sterol regulatory element binding proteins (SREBP). The role gene plays of cholesterol, fatty acid, and glucose metabolism. Indonesia has many several beef cattle which has good quality of growth trait. The aim of this study was to identify polymorphism of INSIG1 gene (SNP 4366 (A>G) and 4534 (T>C)) of three local beef cattle in Indonesia (Bali, Pasundan and Ongole Decendent). One hundred and twenty seven samples were used in this study consisting of Bali cattle (46) from Pulukan Bali Island, Pasundan (36) from UPTD BPPT Beef cattle Ciamis West Java and Ongole Grade (OD) (45). DNA was extracted from whole blood using High Salt method then genotyping used PCR-RFLP method with RsaI and TaqI enzymes. Parameters in this study were genotype and allele frequencies, heterozigosity observed (Ho), expected (He), Hardy-Weinberg Equilibrium (HWE) and Polymorphism Information Content (PIC). Result showed that a 428 bp of DNA fragment was successfully amplified and digested. Three variant of genotypes with two alleles were identified. For SNP 4366 (A>G) were AA, AG and GG with dominant of G allele while SNP 4534 (T>C) were CC, CT and TT with dominant C allele. Both of SNPs in each of breed populations was in Hardy-Weinberg Equilibrium and polymorphic. Additionally, PIC value reached moderate. In conclusion, polymorphism was found in beef cattle and it could be early study for genetic diversity

Genetic polymorphisms of BDNF on cognitive functions in drug-naive first episode patients with schizophrenia

Brain-derived neurotrophic factor (BDNF) is reported to be involved in cognitive decline in patients with schizophrenia (SZ). Previous studies have found that cognitive deficits remain stable during the chronic disease phase in SZ, but the findings were inconsistent. The role of BDNF in cognitive deficits at different stage of illness remains unclear. This study aimed to examine the effect of BDNF polymorphisms on cognitive deficits in drug-naïve first-episode (DNFE) patients and chronic patients with SZ. 262 DNFE patients, 844 chronic patients, and 1043 healthy controls were recruited to compare 4 polymorphisms in BDNF gene and cognitive function. We found that there was no significant difference in genotype and allele frequencies between SZ patients and controls. However, they were closely related to cognitive functioning. BDNF rs2030324 polymorphism played a strong role in language performance only in DNFE patients with SZ. The language index of DNFE patients with rs2030324 TT and TC genotypes was worse than that of chronic patients, but there was no significant difference in CC genotypes between DNFE and chronic patients. Rs6265 had no significant effect on cognitive functioning in patients and controls. Our result suggests BDNF gene polymorphisms were related to different domains of cognitive function at the different stage of SZ, especially language in DNFE patients.

CKM Gene rs8111989 Polymorphism and Power Athlete Status

Multiple genetic variants are known to influence athletic performance. These include polymorphisms of the muscle-specific creatine kinase (CKM) gene, which have been associated with endurance and/or power phenotypes. However, independent replication is required to support those findings. The aim of the present study was to determine whether the CKM (rs8111989, c.*800A>G) polymorphism is associated with power athlete status in professional Russian and Lithuanian competitors. Genomic DNA was collected from 693 national and international standard athletes from Russia (n = 458) and Lithuania (n = 235), and 500 healthy non-athlete subjects from Russia (n = 291) and Lithuania (n = 209). Genotyping for the CKM rs8111989 (A/G) polymorphism was performed using PCR or micro-array analysis. Genotype and allele frequencies were compared between all athletes and non-athletes, and between non-athletes and athletes, segregated according to population and sporting discipline (from anaerobic-type events). No statistically significant differences in genotype or allele frequencies were observed between non-athletes and power athletes (strength-, sprint- and speed/strength-oriented) athletes. The present study reports the non-association of the CKM rs8111989 with elite status in athletes from sports in which anaerobic energy pathways determine success.

Formation of adaptive types as a process of microevolution

The study populations have been grouped into two clusters. The first constituted the ethnic groups that are anthropologically affine but differ in adaptive types and husbandry practices. The second included the anthropologically unrelated ethnic groups having similar environment economy systems and adaptive types. We analyzed the genotype and allele frequencies of the metabolism-associated APOE, LCT, TREH, UCP1 genes, and Fok1 and BsmI polymorphisms of VDR gene. A total of 749 samples in the study represents the ethnic groups of Komi-Permyaks (n=181), Komi (n=235), Komi-Izhems (n=200), Shores (n=133). Results. A resemblance in the morphological and physiological complexes that have convergently developed in the course of environmental adaptations have been shown to reflect similarities in the gene features of anthropologically unrelated populations. In contrast, in the historically related groups that have utilized different biotopes and types of husbandry, there are growing divergence in the frequencies of metabolism-associated genotypes and alleles. These findings imply that ecological adaptations of modern human populations drive the minor changes in allele frequencies, which have occurred over a few generations. Conclusion. The apparent morpho-physiological and population-genetic specificity of the adaptive types allows us to regard the process of their formation as microevolution.

Role of the IL33 and IL1RL1 pathway in the pathogenesis of Immunoglobulin A vasculitis

Cytokines signalling pathway genes are crucial factors of the genetic network underlying the pathogenesis of Immunoglobulin-A vasculitis (IgAV), an inflammatory vascular condition. An influence of the interleukin (IL)33- IL1 receptor like (IL1RL)1 signalling pathway on the increased risk of several immune-mediated diseases has been described. Accordingly, we assessed whether the IL33-IL1RL1 pathway represents a novel genetic risk factor for IgAV. Three tag polymorphisms within IL33 (rs3939286, rs7025417 and rs7044343) and three within IL1RL1 (rs2310173, rs13015714 and rs2058660), that also were previously associated with several inflammatory diseases, were genotyped in 380 Caucasian IgAV patients and 845 matched healthy controls. No genotypes or alleles differences were observed between IgAV patients and controls when IL33 and IL1RL1 variants were analysed independently. Likewise, no statistically significant differences were found in IL33 or IL1RL1 genotype and allele frequencies when IgAV patients were stratified according to the age at disease onset or to the presence/absence of gastrointestinal (GI) or renal manifestations. Similar results were disclosed when IL33 and IL1RL1 haplotypes were compared between IgAV patients and controls and between IgAV patients stratified according to the clinical characteristics mentioned above. Our results suggest that the IL33-IL1RL1 signalling pathway does not contribute to the genetic network underlying IgAV.

BAFF, APRIL and BAFFR on the pathogenesis of Immunoglobulin-A vasculitis

BAFF, APRIL and BAFF-R are key proteins involved in the development of B-lymphocytes and autoimmunity. Additionally, BAFF, APRIL and BAFFR polymorphisms were associated with immune-mediated conditions, being BAFF GCTGT>A a shared insertion-deletion genetic variant for several autoimmune diseases. Accordingly, we assessed whether BAFF, APRIL and BAFFR represent novel genetic risk factors for Immunoglobulin-A vasculitis (IgAV), a predominantly B-lymphocyte inflammatory condition. BAFF rs374039502, which colocalizes with BAFF GCTGT>A, and two tag variants within APRIL (rs11552708 and rs6608) and BAFFR (rs7290134 and rs77874543) were genotyped in 386 Caucasian IgAV patients and 806 matched healthy controls. No genotypes or alleles differences were observed between IgAV patients and controls when BAFF, APRIL and BAFFR variants were analysed independently. Likewise, no statistically significant differences were found in the genotype and allele frequencies of BAFF, APRIL or BAFFR when IgAV patients were stratified according to the age at disease onset or to the presence/absence of gastrointestinal (GI) or renal manifestations. Similar results were disclosed when APRIL and BAFFR haplotypes were compared between IgAV patients and controls and between IgAV patients stratified according to the clinical characteristics mentioned above. Our results suggest that BAFF, APRIL and BAFFR do not contribute to the genetic network underlying IgAV.

The expression and mutation of <i>BMPR1B</i> and its association with litter size in small-tail Han sheep (<i>Ovis aries</i>)

Previous studies have shown that BMPR1B promotes follicular development and ovarian granulosa cell proliferation, thereby affecting ovulation in mammals. In this study, the expression and polymorphism of the BMPR1B gene associated with litter size in small-tail Han (STH) sheep were determined. The expression of BMPR1B was detected in 14 tissues of STH sheep during the follicular phase as well as in the hypothalamic–pituitary–gonadal (HPG) axis of monotocous and polytocous STH sheep during the follicular and luteal phases using quantitative polymerase chain reaction (qPCR). Sequenom MassARRAY® single nucleotide polymorphism (SNP) technology was also used to detect the polymorphism of SNPs in seven sheep breeds. Here, BMPR1B was highly expressed in hypothalamus, ovary, uterus, and oviduct tissue during the follicular phase, and BMPR1B was expressed significantly more in the hypothalamus of polytocous ewes than in monotocous ewes during both the follicular and luteal phases (P<0.05). For genotyping, we found that genotype and allele frequencies of three loci of the BMPR1B gene were extremely significantly different (P<0.01) between the monotocous and polytocous groups. Association analysis results showed that the g.29380965A>G locus had significant negative effects on the litter size of STH sheep, and the combination of g.29380965A>G and FecB (Fec – fecundity and B – Booroola; A746G) at the BMPR1B gene showed that the litter size of AG–GG, AA–GG, and GG–GG genotypes was significantly higher compared with other genotypes (P<0.05). This is the first study to find a new molecular marker affecting litter size and to systematically analyze the expression of BMPR1B in different fecundity and physiological periods of STH sheep.

The Polymorphism in Various Milk Protein Genes in Polish Holstein-Friesian Dairy Cattle

The aim of the present study was to evaluate the genotype and allele frequencies of 24 polymorphisms in casein alpha S1 (CSN1S1), casein alpha S2 (CSN1S2), beta-casein (CSN2), kappa-casein (CSN3), and progestagen-associated endometrial protein (PAEP) genes. The study included 1900 Polish Black and White Holstein-Friesian dairy cows that were subjected to genotyping via microarrays. A total of 24 SNPs (Single Nucleotide Polymorphisms) within tested genes were investigated. Two CSN1S1 SNPs were monomorphic, while allele CSN1S1_3*G in CSN1S1_3 SNP dominated with a frequency of 99.39%. Out of seven CSN2 SNPs, four were polymorphic; however, only for CSN2_3 all three genotypes were detected. Only three out of nine SNPs within CSN3 were monomorphic. Three PAEP SNPs were also found to be polymorphic with heterozygotes being most frequent. Hardy–Weinberg equilibrium (HWE) was observed for eight variants. It was shown that only CSN3_6 was not in HWE. The fact that many of investigated SNPs were monomorphic may suggest that in the past the reproduction program favored one of these genotypes. SNPs that are included in commercially available microarrays should be monitored in relation to changes in their frequencies. If a SNP has turned monomorphic, maybe it should be considered for removal from the microarray.

C-Reactive Protein +1444C/T Polymorphism Is Associated with the Susceptibility to Pulmonary Tuberculosis

Objective. The T allele of C-reactive protein (CRP) +1444C/T (rs1130864) polymorphism was associated with increased risk for some inflammatory conditions. The objective of the study was to explore the association between the CRP +1444C/T polymorphism with the susceptibility to pulmonary tuberculosis (PTB) in a Chinese population. Methods. This case-control study enrolled 480 PTB patients and 480 healthy controls. The CRP +1444C/T polymorphism was determined using Sanger sequencing. The odds ratio (OR) and 95% confidence interval (CI) were assessed to examine the strength of genetic correlation. Results. The genotype and allele frequencies of PTB patients differed from controls (CT vs. CC, OR = 1.924 , 95% CI: 1.099-3.371, adjusted P value = 0.022 ; T vs. C, OR = 1.884 , 95% CI: 1.085-3.273, adjusted P value = 0.024 ). Stratified analysis by sex found that PTB patients’ genotype and allele frequencies differed from controls in the male subgroup but not the female subgroup. Conclusion. In conclusion, the minor T allele of CRP +1444C/T polymorphism was associated with increased PTB risk.