Homozygote Genotype Research Articles

Natural Selection Mediated Association of the Duffy (FY) Gene Polymorphisms with Plasmodium vivax Malaria in India

The Duffy (Fy) antigens act as receptors for chemokines as well as for Plasmodium vivax to invade human RBCs. A recent study has correlated the occurrence of the FY*A allele of Duffy gene with decreased susceptibility to vivax malaria, but no epidemiological correlation between the distribution of FY*A allele and incidences of vivax malaria has been established so far. Furthermore, if such correlations exist, whether natural selection has mediated the association, is an important question. Since India is highly endemic to P. vivax malaria with variable eco-climatic and varying vivax malaria epidemiology across different regions, such a question could well be answered in Indians. For this, we have genotyped the FY gene at the −33rd and the 125th nucleotide positions in 250 Indians sampled from six different zonal plus one tribal population covering the whole of India and studied possible correlations with eco-climatic and vivax malaria incidences. No FY*O allele was found, however, both the FY*A and FY*B alleles forming FY*A/FY*A, FY*A/FY*B and FY*B/FY*B genotypes were widely distributed among Indians. Five out of seven population samples significantly deviated from the Hardy-Weinberg equilibrium expectation, and two alleles (FY*A and FY*B) and the homozygote genotype, FY*B/FY*B were clinally distributed over the population coordinates. Furthermore, vivax malaria incidences over the past five years were significantly negatively and positively associated with the frequencies of the FY*A and FY*B alleles, respectively. The Northern Indians were highly differentiated from the other zonal population samples at the FY gene, as evidenced from the reconstructed Neighbor-Joining phylogenetic tree. The results specify the role of natural selection in the distribution of FY gene polymorphism in India. Furthermore, the hypotheses on the part of the FY*A allele in conferring protection to vivax malaria could be validated following population genetic studies in a vivax malaria epidemiological setting, such as India.

Patterns of angiotensin converting enzyme insertion/deletion gene polymorphism among an Egyptian cohort of patients with rheumatoid arthritis

This case control study was designed to determine the patterns of angiotensin converting enzyme insertion/deletion (ACE I/D) gene polymorphism in rheumatoid arthritis (RA) patients and healthy controls. The study population was divided into two groups: the study group included 66 RA patients diagnosed according to the American College of Rheumatology (ACR) classification criteria for RA, and the control group included 66 healthy adults who were age-and sex-matched to the RA group. All RA patients were assessed by Disease Activity Score (DAS28), ACR Classification of Global Functional Disability Status and Sharp's score as outcome measures. Gene investigations for ACE I/D polymorphism were performed by polymerase chain reaction (PCR) in both groups. The ACE I/D polymorphism was the (D/D) genotype in 60.6% (n = 40) of RA patients, the (I/D) genotype in 31.8% (n = 21) and the (I/I) genotype in 7.6% (n = 5). The frequency of (D) carriage was significantly higher in the RA cases than in the control group (76.5% vs. 53.8%, respectively, P = 0.0002). ACE D allele carriers were at higher risk of RA, 2.8 times higher than (I) carriers and those who had the homozygote (DD) genotype had 5.6 times the possibility of having RA. No correlations were observed between the homozygote (DD) genotype and disease activity or severity in RA patients. Our study suggests that high frequency of the ACE D allele contributes to the heritability of RA susceptibility compared to other ACE alleles. On the other hand, no association was detected between ACE I/D polymorphism and the severity of RA.

Additive and dominance effects of the αs1-casein locus on milk yield and composition traits in dairy goats

The objective of this study was to evaluate the effects of the CSN1S1 locus polymorphism on 305-d records of milk, fat, protein, lactose and total solids yields, fat, protein, lactose and total solids contents in Mexican dairy goats. A total of 514 lactation records belonging to Alpine (n=60), Saanen (n=105) and Toggenburg (n=74) goats, born from 2003 to 2006 in three herds were used. Discrimination between alleles E, F, N, A* (CSN1S1 A, G, H, I, O1 and O2) and B* (CSN1S1 B1, B2, B3, B4, C and L) were made by amplification of fragments of the gene CSN1S1 and digestion with the restriction endonuclease XmnI. In order to estimate additive and dominance effects, data sets including (1) all genotypes, and (2) only homozygote genotypes, were analysed using linear mixed models. The allele A*, had significant additive effects for protein content (0·21±0·07%; P=0·002) and total solids content (0·66±0·23%; P=0·005) when compared with allele F. An unfavourable additive effect of allele A* on milk yield was found in the Alpine breed (-81·4±40·2; P=0·046) when compared with allele F. Favourable dominance effects were found for some genotypes (P<0·05) for milk yield (A*N and B*N), fat yield (A*N and B*E), protein yield (A*N and B*E), lactose yield (A*N) and total solids yield (A*N). Also, unfavourable dominance effects were found (P<0·05) for protein content (A*B* and A*N) and total solids content (A*B*, A*N, and A*F). Allele A* was the only one with a positive effect for protein content. Significant allele-year interaction effects were also observed. The presence of significant dominance effects, estimated between specific pairs of alleles, challenged the purely additive nature of the genetic effect at the CSN1S1 locus. Implications from use of CSN1S1 effects in goat breeding programmes are presented.

A miR-1231 binding site polymorphism in the 3′UTR of IFNAR1 is associated with hepatocellular carcinoma susceptibility

Hepatocellular carcinoma (HCC) is a common liver malignancy worldwide and genetic factors play important roles in the pathogenesis of HCC. Based on in-silico analysis, a case–control study including 420 HCC patients and 420 healthy controls was conducted to investigate the association between HCC susceptibility with a 4-bp insertion/deletion polymorphism (rs17875871) in the 3′UTR of IFNAR1. Computational modeling suggested that rs17875871 was located in seed region of miR-1231 potential target sequence in IFNAR1 3′UTR. Logistic regression analysis showed that the heterozygote and the 4-bp del/del homozygote genotypes confer significantly higher risks of HCC (adjusted OR=1.35, 95% CI=1.01–1.83, P=0.045; OR=1.84, 95% CI=1.18–2.84, P=0.006, respectively). Stratification analysis revealed that this association was more pronounced in HBsAg positive subgroup. Our findings suggested common genetic changes in IFNAR1 may influence HCC risk, likely through miR-1231-mediated regulation, which is possibly involved in the pathogenesis of HBV related HCC. Further replication studies and functional characterization of rs17875871 were needed to fully clarify the underlined molecular mechanism.

NALP1/NLRP1 Genetic Variants are Associated With Alzheimer Disease

Alzheimer disease (AD) is a complex neurodegenerative disease. Genetic and molecular studies have confirmed that in the human brain, amyloid-β fibrils can induce, through the activation of NALP1 inflammosome, inflammatory and apoptotic responses involved in the pathogenesis of AD. Considering that AD pathogenesis is multifactorial, we hypothesized that NALP1/NLRP1 could be a susceptibility gene involved in the devolvement of the disease. The possible association between 9 selected polymorphisms in the NALP1/NLRP1 gene and AD was evaluated by comparing their frequency distribution in an Italian cohort of AD patients (AD, n = 276) and in a group of Italian sex-matched and age-matched healthy controls without dementia (HC, n = 266). Our study, evidences the association of 4 nonsynonymous polymorphisms in the NLRP1 gene (rs2137722, rs34733791, rs11657747, rs11651595) with AD. The major alleles of all 4 single nucleotide polymorphisms and the corresponding homozygote genotypes were more frequent in AD patients than in healthy controls, suggesting an association of these variants in the predisposition versus the development of the disease. These findings seem to support the previously reported role of NALP1 in neuronal damage, and provide evidence of an association between single nucleotide variations in the NLRP1 gene and AD.

Influence of BLK polymorphisms on the risk of rheumatoid arthritis

B cell lymphocyte kinase (BLK) encodes a member of the Src kinase family and thus may influence the proliferation and differentiation of cells. A single nucleotide polymorphism (SNP) located in the first intron of BLK has shown that the risk C allele of rs2248932 is associated with lower levels of messenger RNA expression of BLK. We hypothesized that this polymorphism may contribute to rheumatoid arthritis (RA) susceptibility. We studied BLK rs2248932 T/C gene polymorphisms in 329 patients with RA and 697 controls in a Chinese population. Genotyping was done using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). When the BLK rs2248932 TT homozygote genotype was used as the reference group, the CC genotype was associated with a significantly increased risk of RA. In the recessive model, when the BLK rs2248932 TT/TC genotypes were used as the reference group, the CC homozygote genotype was associated with a significantly increased susceptibility to RA. In stratification analyses, a significantly increased risk for RA associated with the BLK rs2248932 CC genotype was evident among younger patients, CRP-negative patients and anti-CCP-positive patients compared with the BLK rs2248932 TT/TC genotype. The risk was also significantly evident among RF-positive patients, patients with lower ESR levels, patients with lower or higher DAS28 score and patients with a lower functional class. These findings suggested that the functional SNP BLK rs2248932 T/C variant allele was associated with RA development. However, our results were obtained from a moderate-sized sample, and therefore this is a preliminary conclusion. Validation in a larger study from a more diverse ethnic population is needed to confirm these findings.

Effect of Tryptophan Hydroxylase Gene Polymorphism on Aggression in Major Depressive Disorder and Undifferentiated Somatoform Disorder

Aggression and anger have been linked with depression, and anger suppression has been linked with somatic symptoms of somatoform disorders. However, the relationship between aggression or anger and genes in patients with depression and somatoform disorders has not been clearly elucidated. The objective of this study was to examine the effect of serotonin-related gene polymorphism on aggression in depressive disorders and somatoform disorders. A serotonin-related polymorphic marker was assessed by using single nucleotide polymorphism (SNP) genotyping. 106 outpatients with major depressive disorder (MDD), 102 outpatients with undifferentiated somatoform disorder, and 133 healthy subjects were enrolled between October 2005 and May 2008. Diagnoses were made according to the Korean version of the Structured Clinical Interview Schedule for DSM-IV. The allele and genotype frequencies of tryptophan hydroxylase-1 (TPH1) A218C were compared between groups. The Hamilton Depression Rating Scale and the Aggression Questionnaire were used for psychological assessment. Each of the 2 disorder groups scored significantly higher on all the Aggression Questionnaire subscales and on the total Aggression Questionnaire score than the healthy subjects (P < .001). Patients with MDD had significantly higher frequencies of TPH1 C allele (P = .0002) and CC homozygote (P = .0003) than healthy subjects, regardless of sex and age. However, no significant differences were found in TPH1 C allele and CC homozygote frequencies between the undifferentiated somatoform disorder patients and the healthy subjects. TPH1 CC homozygote in the MDD group scored significantly higher in terms of verbal aggression (P = .03) and total Aggression Questionnaire score (P = .04) than A-carrier genotypes, regardless of sex and age. However, no significant differences were found in the scores of all the Aggression Questionnaire subscales and the total Aggression Questionnaire score between TPH1 CC homozygote and A-carrier genotypes in the undifferentiated somatoform disorder group and the control group, respectively. Aggression in MDD patients is more susceptible to an excess of TPH1 CC homozygote than in undifferentiated somatoform disorder patients, though the 2 disorders are high risk groups for aggression. In addition, TPH1 gene is most likely to have a shared effect on aggression and MDD.

Association of PHB 1630 C>T and MTHFR 677 C>T polymorphisms with breast and ovarian cancer risk in BRCA1/2 mutation carriers: results from a multicenter study.

Background:The variable penetrance of breast cancer in BRCA1/2 mutation carriers suggests that other genetic or environmental factors modify breast cancer risk. Two genes of special interest are prohibitin (PHB) and methylene-tetrahydrofolate reductase (MTHFR), both of which are important either directly or indirectly in maintaining genomic integrity.Methods:To evaluate the potential role of genetic variants within PHB and MTHFR in breast and ovarian cancer risk, 4102 BRCA1 and 2093 BRCA2 mutation carriers, and 6211 BRCA1 and 2902 BRCA2 carriers from the Consortium of Investigators of Modifiers of BRCA1 and BRCA2 (CIMBA) were genotyped for the PHB 1630 C>T (rs6917) polymorphism and the MTHFR 677 C>T (rs1801133) polymorphism, respectively.Results:There was no evidence of association between the PHB 1630 C>T and MTHFR 677 C>T polymorphisms with either disease for BRCA1 or BRCA2 mutation carriers when breast and ovarian cancer associations were evaluated separately. Analysis that evaluated associations for breast and ovarian cancer simultaneously showed some evidence that BRCA1 mutation carriers who had the rare homozygote genotype (TT) of the PHB 1630 C>T polymorphism were at increased risk of both breast and ovarian cancer (HR 1.50, 95%CI 1.10–2.04 and HR 2.16, 95%CI 1.24–3.76, respectively). However, there was no evidence of association under a multiplicative model for the effect of each minor allele.Conclusion:The PHB 1630TT genotype may modify breast and ovarian cancer risks in BRCA1 mutation carriers. This association need to be evaluated in larger series of BRCA1 mutation carriers.

Association between polymorphic sites in thymidylate synthase gene and risk of non-Hodgkin lymphoma: a systematic review and pooled analysis

Epidemiological studies have evaluated the association between polymorphic sites in the thymidylate synthase (TYMS) gene and non-Hodgkin lymphoma (NHL) risk, but the results remain controversial. Here we performed a meta-analysis to estimate the relationship between TYMS polymorphisms and the risk of NHL and two of its subtypes from all nine published case–control studies. Our meta-analysis suggested that both 1053C > T and IVS6-68C >T polymorphisms were significantly associated with decreased risks of NHL among Caucasians (for 1053C > T: TT vs. CC, odds ratio [OR] = 0.78, 95% confidence interval [CI] = 0.64–0.95; recessive model, OR = 0.81, 95% CI = 0.67–0.98 and for IVS6 - 68C > T: TT vs. CC, OR = 0.61, 95% CI = 0.40–0.92; recessive model, OR = 0.63, 95% CI = 0.42–0.93), whereas the TSER, 1122A > G and 1494del6 polymorphisms had no influence on the susceptibility to NHL. Further analysis revealed that the T allele of the 1053C > T polymorphism might provide protective effects in Caucasians against the risk of NHL (OR = 0.90, 95% CI = 0.82–0.98) and follicular lymphoma (FL) (OR = 0.81, 95% CI = 0.71–0.93), but not diffuse large B-cell lymphoma (DLBCL). Additionally, the IVS6 - 68C > T variant homozygote genotype was significantly associated with reduced risks for DLBCL (TT vs. CC: OR = 0.51, 95% CI = 0.28–0.94; recessive model: OR = 0.53, 95% CI = 0.29–0.96), but not FL. However, individuals carrying the T allele of the IVS6 - 68C > T polymorphism were not significantly associated with reduced risks for DLBCL and FL.

Peptidylarginine Deiminase Type 4 and Methyl-CpG Binding Domain 4 Polymorphisms in Chinese Patients with Rheumatoid Arthritis

Peptidylarginine deiminase type 4 (PADI4) and methyl-CpG binding domain 4 (MBD4) are closely related with rheumatoid arthritis (RA). We hypothesized that PADI4 and MBD4 polymorphisms may contribute to RA susceptibility. We studied PADI4 rs2240340 G/A, PADI4 rs874881 C/G, MBD4 rs140693 G/A, and MBD4 rs2005618 T/C gene polymorphisms in 329 patients with RA and 697 controls in a Chinese population. Genotyping was done using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). When the PADI4 rs2240340 GG homozygote genotype was used as the reference group, the AA genotype was associated with a significantly increased risk of RA. In the recessive model, when PADI4 rs2240340 GG/GA genotypes were used as the reference group, the AA homozygote genotype was associated with a significant increased susceptibility to RA. PADI4 rs874881 C/G was in complete linkage disequilibrium with PADI4 rs2240340 G/A. MBD4 rs140693 G/A and MBD4 rs2005618 T/C polymorphisms were not associated with the risk of RA. In stratification analyses, a significantly increased risk for RA associated with the PADI4 rs2240340 AA genotype was evident among older patients and patients who were anticitrullinated protein antibody (ACPA)-positive compared with the PADI4 rs2240340 GG/GA genotype. These findings suggest that the functional single-nucleotide polymorphism PADI4 rs2240340 G/A variant allele is associated with RA development, especially among older patients and ACPA-positive patients. However, our results were obtained from a moderate-sized sample, and therefore this is a preliminary conclusion. Validation by a larger study from a more diverse ethnic population is needed to confirm these findings.

Effect of polymorphic variants of GH, Pit-1, and β-LG genes on milk production of Holstein cows

Effect of polymorphic variants of growth hormone (GH), beta-lactoglobulin (beta-LG), and Pit-1 genes on milk yield was analyzed in a Holstein herd. Genotypes of the cows for these genes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Allele frequencies were 0.884 and 0.116 for L and V variants of GH, 0.170 and 0.830 for A and B variants of Pit-1, and 0.529 and 0.471 for A and B variants of beta-LG, respectively. GLM procedure of SAS software was used to test the effects of these genes on milk yield. Results indicated significant effects of these genes on milk yield (P < 0.05). Cows with LL genotype of GH produced more milk than cows with LVgenotype (P < 0.05). Also, for Pit-1 gene, animals with AB genotype produced more milk than BB genotype (P < 0.05). In the case of beta-LG gene, milk yield of animals with AA genotype was more than BB genotype (P < 0.01). Therefore, it might be concluded that homozygote genotypes of GH (LL) and beta-LG (AA) were superior compared to heterozygote genotypes, whereas, the heterozygote genotype of Pit-1 gene (AB) was desirable.

IRAK1 rs3027898 C/A polymorphism is associated with risk of rheumatoid arthritis

IRAK1 and miR-499 play an important role in the etiology of rheumatoid arthritis. Few studies to date have focused on the influence of the IRAK1 rs3027898 C/A and hsa-mir-499 rs3746444 T/C polymorphisms in the susceptibility of the Chinese population to rheumatoid arthritis. We hypothesized that these polymorphisms may contribute to rheumatoid arthritis susceptibility. We studied IRAK1 rs3027898 C/A and hsa-mir-499 rs3746444 T/C gene polymorphisms in 214 rheumatoid arthritis cases and 478 controls in a Chinese population. Genotyping was performed by using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). When the IRAK1 rs3027898 CC homozygote genotype was used as the reference group, the AA genotype was associated with significantly increased risk of rheumatoid arthritis (odds ratio (OR) = 1.91, 95 % confidence interval (CI) = 1.12-3.26, p = 0.017). A significantly increased risk of RA associated with the IRAK1 rs3027898 AA genotype was more evident among females, younger patients, CRP negative patients and both anti-CCP positive and negative patients compared with the IRAK1 rs3027898 CC/CA genotypes. The hsa-mir-499 rs3746444 T/C single nucleotide polymorphism (SNP) was not significantly associated with the risk for rheumatoid arthritis. Our findings suggest that the functional SNP IRAK1 rs3027898 C/A variant allele is associated with the development of rheumatoid arthritis. However, the hsa-mir-499 rs3746444 T/C polymorphism may not be associated with susceptibility to rheumatoid arthritis.

EPHA2 Polymorphisms and Age-Related Cataract in India

ObjectiveWe investigated whether previously reported single nucleotide polymorphisms (SNPs) of EPHA2 in European studies are associated with cataract in India.MethodsWe carried out a population-based genetic association study. We enumerated randomly sampled villages in two areas of north and south India to identify people aged 40 and over. Participants attended a clinical examination including lens photography and provided a blood sample for genotyping. Lens images were graded by the Lens Opacification Classification System (LOCS III). Cataract was defined as a LOCS III grade of nuclear ≥4, cortical ≥3, posterior sub-capsular (PSC) ≥2, or dense opacities or aphakia/pseudophakia in either eye. We genotyped SNPs rs3754334, rs7543472 and rs11260867 on genomic DNA extracted from peripheral blood leukocytes using TaqMan assays in an ABI 7900 real-time PCR. We used logistic regression with robust standard errors to examine the association between cataract and the EPHA2 SNPs, adjusting for age, sex and location.Results7418 participants had data on at least one of the SNPs investigated. Genotype frequencies of controls were in Hardy-Weinberg Equilibrium (p>0.05). There was no association of rs3754334 with cataract or type of cataract. Minor allele homozygous genotypes of rs7543472 and rs11260867 compared to the major homozygote genotype were associated with cortical cataract, Odds ratio (OR) = 1.8, 95% Confidence Interval (CI) (1.1, 3.1) p = 0.03 and 2.9 (1.2, 7.1) p = 0.01 respectively, and with PSC cataract, OR = 1.5 (1.1, 2.2) p = 0.02 and 1.8 (0.9, 3.6) p = 0.07 respectively. There was no consistent association of SNPs with nuclear cataract or a combined variable of any type of cataract including operated cataract.ConclusionsOur results in the Indian population agree with previous studies of the association of EPHA2 variants with cortical cataracts. We report new findings for the association with PSC which is particularly prevalent in Indians.

AIB1 polymorphisms with breast cancer susceptibility: a pooled analysis of variation in BRCA1/2 mutation carriers and non–carriers

The AIB1 gene (amplified in breast cancer 1), coding for a member of steroid receptor co-activator p160 protein family is involved in regulation of estrogen receptor transactivation influencing the estrogen-dependent gene expression. It contains a glutamine repeat polymorphism and several single nucleotide polymorphisms that may alter the transcriptional activation of the receptor and affect susceptibility to breast cancer. Previous studies have shown that these polymorphisms may modify the breast cancer risk in women carrying BRCA1/2 mutations. However, the results remained controversial. This meta-analysis of literatures was performed to derive a more precise estimation of the relationship. A total of 22 studies were identified, including 3,742 cases and 3,491 controls for AIB1 polyglutamine repeat polymorphism, 2,170 cases and 3,309 controls for Q586H polymorphism, and 2,183 cases and 3,319 controls for T960T polymorphism. Overall, we found no evidence of association for individuals who carried at least one AIB1 allele of 28 or 29 or more repeat with breast cancer risk. But we found increased breast cancer risk in BRCA1/2 mutation carriers for individuals with both alleles ≥29 polyglutamine repeat (OR, 1.64; 95% CI 1.24-2.17). And reduced risk was found to be associated with the Q586H polymorphism among the variant homozygote genotype carriers (OR, 0.42; 95% CI 0.23-0.77). Our results do not support the direct association of AIB1 polyglutamine repeat length and breast cancer. However, we found that BRCA1/2 mutation carriers with both alleles ≥29 repeats have a higher risk of breast cancer.

Influence of MIF, CD40, and CD226 polymorphisms on risk of rheumatoid arthritis

Macrophage migration inhibitory factor (MIF) is a key pro-inflammatory mediator. It plays an important role part in the pathogenesis of several inflammatory and immune diseases. A functional single nucleotide polymorphism (SNP) of MIF -173 G/C is known to influence MIF promoter activity in T lymphoblast cell lines and is associated with a higher serum MIF level. The CD40 is also crucial for some relevant functions of the immune system and may be related to rheumatoid arthritis (RA). And CD226 is an important cell-surface receptor molecule involved in the adhesion and activation of T-cell. We hypothesized that these polymorphisms may contribute to RA susceptibility. We studied MIF -173 G/C, CD40, and CD226 gene polymorphisms in 214 patients with RA and 478 controls in a Chinese population. Genotyping was done by using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). When the MIF -173 GG homozygote genotype was used as the reference group, the CC genotype was associated with a significantly increased risk for RA. In the recessive model, when the MIF -173 GG/GC genotypes were used as the reference group, the CC homozygote genotype was associated with a significant 1.56-fold increased susceptibility to RA. None of the CD40 rs1883832 C/T and CD226 rs763361 C/T polymorphisms achieved a significant difference in genotype distributions between cases and controls. In the stratification analyzes, a significantly increased risk for RA associated with the MIF -173 CC genotype was evident among CRP-negative patients compared with the MIF -173 GG/GC genotype. For the CD40 rs1883832 C/T variant, the risk effects of CD40 rs1883832 TT versus CD40 rs1883832 CC/CT were significant in men. These findings suggested that the functional SNP MIF -173 G/C variant allele was associated with the development of RA. However, CD40 and CD226 gene polymorphisms may not be associated with RA susceptibility. Due to the limitation of sample size, this study should be considered preliminary.

Investigation of Polymorphic Variants ofPPARDandAPOEGenes in Turkish Coronary Heart Disease Patients

The aim of this study was to determine the role of polymorphic variants of apolipoprotein E (APOE) and peroxisome proliferator-activated receptor delta (PPARD) genes in the development of coronary heart disease (CHD), and the PPARD and APOE gene-gene interaction in a Turkish population. This study was carried out using a sample of 223 patients with CHD (103 with diabetes and 120 without diabetes) and 101 controls. PPARD +294T/C and APOE genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism technique. The PPARD and APOE genotype distributions were the same between study groups (p>0.05). In the nondiabetic CHD patients, the PPARD +294 C allele showed higher serum low-density lipoprotein cholesterol (LDL-C) level than the common +294 TT homozygote genotype (3.83 ± 1.01 vs. 3.33 ± 1.14, p=0.015). In addition, a significant association between APOE 4 and PPARD +294 C alleles was detected based on their effects on LDL-C in the nondiabetic CHD patients (+294 C/APOE4: 4.43 ± 0.88 vs. +294 TT/nonAPOE 4: 3.48 ± 1.09, p = 0.009). This association indicated the interaction of two genes on plasma LDL-C levels ascended in the order +294 T<+294 T-APOE 4<+294 C<APOE 4<+294 C-APOE 4. The PPARD +294 C allele was associated with higher incidence of left ventricular hypertrophy (LVH) in all male patients with body mass index >27. In addition, the CHD patients who were +294 C allele carriers had a 2.48-fold higher risk of LVH than subjects homozygous for the T allele. An increasing effect of the PPARD +294 C allele was shown on serum LDL-C levels in nondiabetic CHD patients. In addition, the results suggested that the +294 C allele might be associated with an increased LVH risk especially in male CHD patients. Furthermore, gene-gene interaction between the PPARD +294T/C and the APOE polymorphisms was observed regarding LDL-C concentrations.

Sequence variants in the bovine PRDM16 gene associated with body weight in Chinese cattle breeds

As a zinc-finger protein, PR domain containing 16 (PRDM16) controls brown fat determination by stimulating brown fat cell production while suppressing the expression of genes for production of white fat cells; mutations in this domain are associated with myelodysplastic syndrome and leukemogenesis. In our study, polymorphisms in exons 2, 3, 4, 5, 7, 8, and 9 of the PRDM16 gene were detected by PCR-SSCP, DNA sequencing and CRS-PCR-RFLP methods in 1031 cattle of the Chinese breeds: Jiaxian, Nanyang, Qinchuan, and Chinese Holstein. Three mutations (NC_007314.3: g.577 G>T, 614 T>C, 212237 T>C) were detected. Animals with the homozygote genotype had lower body weight and average daily gain than those with the other genotypes. PRDM16 gene-specific SNPs may be useful markers for growth traits for marker-assisted selection programs.

The significance of Exonuclease 1 K589E polymorphism on hepatocellular carcinoma susceptibility in the Turkish population: a case–control study

Exonuclease 1 (Exo 1) is an important nuclease involved in mismatch repair system that contributes to maintain genomic stability, to modulate DNA recombination, and to mediate cell cycle arrest. A guanine (G)/adenine (A) common single nucleotide polymorphism at first position of codon 589 in Exo 1 gene determines a glutamic acid (Glu, E) to lysine (Lys, K) (K589E) aminoacidic substitution which may alter cancer risk by influencing the activity of Exo 1 protein. Exo 1 K589E polymorphism has been studied in various cancers, but its association with hepatocellular carcinoma (HCC) has yet to be investigated. To determine the association of the Exo 1 K589E polymorphism with the risk of HCC development in a Turkish population, a hospital-based case-control study was designed consisting of 224 subjects with HCC and 224 cancer-free control subjects matched for age, gender, smoking and alcohol status. The genotype frequency of the Exo 1 K589E polymorphism was determined by using a polymerase chain reaction-restriction fragment length polymorphism assay. Our data shows that the Lys/Lys genotype of the Exo 1 K589E polymorphism is associated with increased risk of HCC development in this Turkish population [odds ratio (OR)=2.15, 95% confidence interval (CI): 1.13-4.09, P=0.02]. Furthermore, according to stratified analysis, a significant association was observed between the homozygote Lys/Lys genotype and HCC risk in the subgroups of male gender (OR=2.67, 95% CI: 1.27-5.61, P=0.009) and patients with non-viral-related HCC (OR=3.14, 95% CI: 1.09-8.99, P=0.03). Because our results suggest for the first time that the Lys/Lys homozygote genotype of Exo 1 K589E polymorphism may be a genetic susceptibility factor for HCC in the Turkish population, further independent studies are required to validate our findings in a larger series, as well as in patients of different ethnic origins.

Interleukin-4 receptor alpha polymorphisms in autoimmune myasthenia gravis in a Caucasian population

Autoimmune myasthenia gravis is a T-cell-dependent, antibody-mediated, rare neuromuscular disorder. Interleukin-4, acting via interleukin-4 receptor alpha, plays a pivotal role in B-cell differentiation and antibody production and has been implicated to influence disease progression in experimental autoimmune myasthenia gravis. Polymorphisms of the interleukin-4 receptor alpha gene have been shown to be associated with various autoimmune diseases. We compared the distribution of three polymorphisms of the interleukin-4 receptor alpha gene (S503P, rs1805015, Q576R, rs1801275, I75V, rs1805010), all affecting interleukin-4 signaling, in two cohorts of myasthenia gravis patients with ethnically matched controls. Although the distribution of the S503P and Q576R polymorphisms did not differ significantly between the groups, the frequency of the GG rare homozygote genotype of the I75V polymorphism was significantly higher in patients with myasthenia gravis. Our data suggest that the reduced responsiveness to interleukin-4 because the I75V polymorphism may contribute to the pathogenesis of myasthenia gravis.

The expert system of genotype discrimination for D5S818 locus based on near-infrared spectroscopy–principal discriminant variate

This paper studied the expert system of genotype discrimination for the STR locus D5S818 based on near-infrared spectroscopy–principal discriminant variate (PDV). Six genotypes, i.e. genotypes 10–10, 10–11, 11–11, 11–12, 11–13 and 13–13, were selected as research subjects. Based on the optimum polymerase chain reaction (PCR) conditions, about 54 measuring samples for each genotype were obtained; these samples were tested by near-infrared spectroscopy directly. With differences between homozygote genotypes and heterozygote ones, and differences of the total number of core repeat units between the six genotypes, two types of genotyping-tree structure were constructed and their respective PDV models were studied using the near-infrared spectra of the samples as recognition variables. Finally, based on the classification ability of these two genotyping-tree structures, an optimum expert system of genotype discrimination was built using the PDV models. The result demonstrated that the built expert system had good discriminability and robustness; without any preprocessing for PCR products, the six genotypes studied could be discriminated rapidly and correctly. It provided a methodological support for establishing an expert system of genotype discrimination for all genotypes of locus D5S818 and other STR loci.