Genetic variation in nucleotide excision repair pathway genes influence prostate and bladder cancer susceptibility in North Indian population

BACKGROUND:

Inherited polymorphisms of XPD and XPC genes may contribute to subtle variations in NER DNA repair capacity and genetic susceptibility to development of urological cancer such as prostate and bladder cancer.

MATERIALS AND METHODS:

We genotyped four Single Nucleotide Polymorphs (SNPs) of the DNA repair gene XPD and XPC in 195 prostate cancer (PCa) and 212 bladder cancer (BC) patients and 250 healthy controls from the same area. XPD Exon 10 (G>A) by amplification refractory mutation system and Exon 23 (A>C), XPC Intron 9 (Ins/Del) and Exon 15 (A>C) were genotyped by PCR-RFLP.

RESULTS:

Variant genotype of XPC demonstrated association with PCa as well as in BC (P, 0.013; P, 0.003). Combined genotype (GA+AA) revealed association with PCa and in BC (P, 0.012, P, 0.002). Variant allele also demonstrated risk in both the cancer. Diplotype of XPD and XPC was associated with a significant increase in PCa and BC risk. Variant (+/+) genotype of XPC intron 9 shown increased risk with PCa and in BC (P, 0.012; P, 0.032). CC genotype of XPC exon 15 revealed increase risk (P, 0.047) with PCa not in BC. In clinopathological grade variant allele of XPC intron 9 and 15 demonstrated risk with high grade of tumor and bone metastasis of PCa. In BC variant allele of XPD exon 10 and 15 also shown association with tumor grade. XPC intron 9 influences the risk of BC in former tobacco users in BC.

CONCLUSIONS:

Our result support that SNPs in XPD and XPC gene may reduce NER repair capacity and play a major role for PCa and BC in North India.     

MTHFR Gene variants C677T, A1298C and association with Down syndrome: A Case-control study from South India

BACKGROUND:

The 5,10-methylenetetrahydrofolate reductase (MTHFR) polymorphisms and low folate levels are associated with inhibition of DNA methyltransferase and consequently DNA hypomethylation. The expanding spectrum of common conditions linked with MTHFR polymorphisms includes certain adverse birth outcome, pregnancy complications, cancers, adult cardiovascular diseases and psychiatric disorders, with several of these associations remaining still controversial. Trisomy 21 or Down syndrome (DS) is the most common genetic cause of mental retardation. It stems predominantly from the failure of chromosome 21 to segregate normally during meiosis. Despite substantial research, the molecular mechanisms underlying non-disjunction leading to trisomy 21 are poorly understood.

MATERIALS AND METHODS:

Two common variants C677T and A1298C of the MTHFR gene were screened in 36 parents with DS children and 60 healthy couples from Tamil Nadu and Karnataka. The MTHFR genotypes were studied by RFLP analysis of PCR-amplified products and confirmed by sequencing.

RESULTS:

The CT genotype was seen in three each (8.3%) of case mothers and fathers. One case father showed TT genotype. All the control individuals exhibited the wild type CC genotype. A similar frequency for the uncommon allele C of the second polymorphism was recorded in case mothers (0.35) and fathers (0.37) in comparison with the control mothers (0.39) and fathers (0.37).

CONCLUSION:

This first report on MTHFR C677T and A1298C polymorphisms in trisomy 21 parents from south Indian population revealed that MTHFR 677CT polymorphism was associated with a risk for Down syndrome.     

Gly460Trp polymorphism of the ADD1 gene and essential hypertension in an Indian population: A meta-analysis on hypertension risk

BACKGROUND:

Essential hypertension is a complex genetic trait. Genetic variant of alpha adducin (ADD1) gene have been implicated as a risk factor for hypertension. Given its clinical significance, we investigated the association between ADD1 Gly460Trp gene polymorphism and essential hypertension in an Indian population. Further, a meta-analysis was carried out to estimate the risk of hypertension.

METHODS:

In the current study, 432 hypertensive cases and 461 healthy controls were genotyped for the Gly460Trp ADD1 gene polymorphism. Genotyping was determined by real time PCR using Taqman assay. Multiple logistic regression analysis was used to detect the association between Gly460Trp polymorphism and hypertension.

RESULTS:

No significant association was found in the genotype and allele distribution of Gly460Trp polymorphism with hypertension in our study. A total of 15 case-control studies were included in the meta-analysis. There was no evidence of the association of Gly460Trp polymorphism with hypertension in general or in any of the sub group.

CONCLUSIONS:

We found that the Gly460Trp polymorphism is not a risk factor for essential hypertension in a south Indian Tamilian population. However, the role of ADD1 polymorphism may not be excluded by a negative association study. Further, large and rigorous case-control studies that investigate gene–gene–environment interactions may generate more conclusive claims about the molecular genetics of hypertension.     

The NQO1 allelic frequency in hindu population of central India varies from that of other Asian populations

CONTEXT:

The enzymes encoded by the polymorphic genes NAD (P) H: quinone oxidoreductase 1 (NQO1) play an important role in the activation and inactivation of xenobiotics. This enzyme has been associated with xenobiotic related diseases, such as cancer, therapeutic failure and abnormal effects of drugs.

AIM:

The aim of the present study was to determine the allelic and genotypic frequencies of NQO Hinf I polymorphisms in a Hindu population of Central India.

SETTINGS AND DESIGN:

Polymorphisms of NQO1 were determined in 311 unrelated Hindu individuals.

MATERIALS AND METHODS:

Polymerase chain reaction- Restriction Fragment Length Polymorphism (PCR-RFLP) analysis in peripheral blood DNA for NQO1 Hinf I polymorphism was used in 311 unrelated Hindu individuals.

STATISTICAL ANALYSIS:

Allele frequencies were calculated by direct counting. Hardy Weinberg Equilibrium was evaluated using a Chi-square goodness of fit test.

RESULTS:

The observed allelic frequency was 81% for C (wild) and 19% for T (mutant) in the total sample.

CONCLUSIONS:

The allelic frequency of “C” was higher than in other Asians (57%), but similar to Caucasians (81%). The genotype distributions for Hinf I polymorphisms were in Hardy-Weinberg equilibrium.     

Effect of maternal Tp53 gene G412C polymorphism on neural tube defects: A study from North India

CONTEXT:

Tumor protein 53 (tp53) is one of the candidate gene proposed for neural tube defects, which affects central nervous system during early embryonic development, on the basis of mouse models.

AIMS:

The present study is an attempt to unfold the possible role of tp53 G412C polymorphism in the incidence of neural tube defect (NTDs) in humans.

SETTINGS AND DESIGN:

Case-control study was carried out in government hospitals of Delhi, India.

MATERIALS AND METHODS:

Subjects comprised of 100 mothers of NTD children and 100 matched control mothers. Information on some environmental exposures was collected along with blood samples. After DNA extraction, the genotyping of tp53 G412C polymorphism was carried out by PCR-RFLP method.

Statistical Analysys:

Fisher Exact or Chi square test, binary logistic model, and odds ratio (95% confidence interval) calculations were used to evaluate effect of risk factors on NTDs using SPSS v17.0.

RESULTS:

The ‘CC’ genotype of tp53 G412C showed protective effect towards the development of anencephaly and/or encephalocele (OR: 0.44; 95% CI: 0.19-1.00); however, no significant difference among overall NTD cases and controls was observed (P>0.05). Further segregation of all subjects based on 2 different communities, Hindus and Muslims, the association of ‘CC’ genotype of the polymorphism with reduced NTD risk was observed among Hindu community (OR: 0.33; 95% CI: 0.13-0.79).

CONCLUSION:

The study highlights the selective advantage provided by maternal ‘CC’ genotype, thereby reducing risk of cephalic NTDs, probably due to the lower apoptotic activity of the protein, however, more specifically in the presence of community-specific microenvironment.     

Genetic analysis of OCT1 gene polymorphisms in an Indian population

BACKGROUND:

Genetic variants of the organic cation transporter (OCT1) gene could influence interindividual variation in clinical response to metformin therapy. The genetic basis for the single-nucleotide polymorphism (SNP) of OCT1 gene has been established in other populations, but it remains to be elucidated in the Indian population. This study is focused on OCT1 gene variants rs2282143 (P341L, 1022C>T), rs628031 (M408V, 1222A>G) and rs622342 (1386C>A) frequency distributions in the South Indian Tamilian population.

MATERIALS AND METHODS:

A total of 112 unrelated healthy subjects of South Indian Tamilian origin, aged 18–60 years, of either sex were recruited for the study. Genotyping was determined using the quantitative real time-polymerase chain reaction and polymerase chain reaction followed by restriction fragment length polymorphism methods.

RESULTS:

Allele frequencies of rs2282143, rs628031and rs622342 polymorphisms were 8.9%, 80.3% and 24.5%, respectively. Interethnic differences in the genotype and allele frequencies of OCT1 gene polymorphism were observed when compared with other major populations. The SNPs rs2282143, T allele and rs628031, G allele were more common in Asians (5.5–16.8% and 76.2–81%) and African Americans (8.2% and 73.5%) than in Caucasians (0–2% and 57.4–60%).

CONCLUSION:

This is the first time the frequency of OCT1 gene polymorphism was determined in the Indian population, and is similar to the frequencies observed in African-Americans and other Asian populations but different from those in Caucasians. The data observed in this study would justify further pharmacogenetic studies to potentially evaluate the role of OCT1 gene polymorphism in the therapeutic efficacy of metformin.     

CD14 C-159T polymorphism and its association with chronic lung diseases: A pilot study on isocyanate exposed population of Central India

CONTEXT:

CD14 functions as a multifunctional receptor for bacterial cell wall components including endotoxin and lipopolysaccharide and is likely to influence the cytokine profile and subsequent immunoglobulin E production in response to antigen/allergen contact in allergic phenotypes.

AIMS:

The present study was to investigate genetic polymorphism in CD14 gene - 159C/T, which may be one of the risk factor for increased prevalence of Chronic Lung Diseases in the Central India.

SETTINGS AND DESIGN:

Survivors of Methyl isocyanates toxicity in Bhopal still suffering from various respiratory ailments were examined.

MATERIALS AND METHODS:

Polymerase chain reaction-restriction fragment length polymorphism was performed to determine the polymorphism of C-159T.

RESULTS:

The genotype and allelic frequencies were in Hardy-Weinberg’s equilibrium. Prevalence of CC, CT, and TT were 5.5%, 22.2% and 9.25% respectively in asthmatics; 16.6%, 20.3% and 5.5% respectively in chronic obstructive pulmonary disease (COPD) patients and 5.5%, 14.8% and 1.85 respectively among interstitial lung disorder (ILD) patients; whereas the control cohort with no methyl isocyanate exposure displayed (CC, CT, and TT) cytosine, thymine as 2%, 1.6% and 2% respectively. Increased risk of Asthma among those carrying TT genotype and T allele (odds ratio [OR] =2.61 and 2.02 respectively).

CONCLUSION:

COPD risk significantly found among those with CC genotype and C allele (OR = 2.81 and 1.50 respectively), whereas ILD risk found significantly among CT genotype and C allele (OR = 1.75 and 1.40 respectively). Therefore, single nucleotide polymorphism (SNP) C-159T polymorphism in CD14 gene might be a risk factor for development of CLD in this population.     

Genetic associations of body composition,flexibility and injury risk with ACE,ACTN3 and COL5A1 polymorphisms in Korean ballerinas

[Purpose]

The purpose of this study was to exam the association of body composition, flexibility, and injury risk to genetic polymorphisms including ACE ID, ACTN3 RX, and COL5A1 polymorphisms in ballet dancers in Korea.

[Methods]

For the purpose of this study, elite ballerinas (n = 97) and normal female adults (n = 203) aged 18 to 39 were recruited and these participants were tested for body weight, height, body fat, fat free mass, flexibility, injury risks on the joints and gene polymorphisms (ACE, ACTN3, COL5A1 polymorphism).

[Results]

As results, the ACE DD genotype in ballerinas was associated with higher body fat and percentage of body fat than the ACE II and ID genotypes (p < 0.05). In the study on the ACTN3 polymorphism and ballerinas, the XX genotype in ballerinas had lower body weight and lower fat-free mass than the RR and RX genotype (p < 0.005). Also, the means of sit and reach test for flexibility was lower in the ACTN3 XX genotype of ballerinas than the RR and RX genotype of ballerinas (p < 0.05). Among the sports injuries, the ankle injury of the XX-genotyped ballerinas was in significantly more prevalence than the RR and XX-genotyped ballerinas (p < 0.05). According to the odd ratio analysis, XX-genotyped ballerinas have the injury risk on the ankle about 4.7 (95% CI: 1.6~13.4, p < 0.05) times more than the RR and RX-genotyped ballerinas. Meanwhile, the COL5A1 polymorphism in ballerinas has no association with any factors including flexibility and injury risks.

[Conclusion]

In conclusion, ACE polymorphism and ACTN3 polymorphism were associated with ballerinas'' performance capacity; COL5A1 was not associated with any factors of performance of Ballerinas. The results suggested that the ACE DD genotype is associated with high body fat, the ACTN3 XX genotype is associated with low fat-free mass, low flexibility, and higher risk of ankle-joint injury.     

p21 rs3176352 G>C and p73 rs1801173 C>T Polymorphisms Are Associated with an Increased Risk of Esophageal Cancer in a Chinese Population

Objective

Esophageal cancer was the fifth most commonly diagnosed cancer and the fourth leading cause of cancer-related death in China in 2009. Genetic factors might play an important role in esophageal squamous cell carcinoma (ESCC) carcinogenesis.

Designs and Methods

To evaluate the effect p21, p53, TP53BP1 and p73 single nucleotide polymorphisms (SNPs) on the risk of ESCC, we conducted a hospital based case–control study. A total of 629 ESCC cases and 686 controls were recruited. Their genotypes were determined using ligation detection reaction (LDR) method.

Results

When the p21 rs3176352 GG homozygote genotype was used as the reference group, the CC genotype was associated with a significantly increased risk of ESCC. When the p73 rs1801173 CC homozygote genotype was used as the reference group, the CT genotype was associated with a significantly increased risk of ESCC. After Bonferroni correction, for p21 rs3176352 G>C, the p _correct was still significant. For the other six SNPs, in all comparison models, no association between the polymorphisms and ESCC risk was observed.

Conclusions

p21 rs3176352 G>C and p73 rs1801173 C>T SNPs are associated with increased risk of ESCC. To confirm the current findings, additional, larger studies and tissue-specific biological characterization are required.     

Risk conferred by FokI polymorphism of vitamin D receptor (VDR) gene for essential hypertension

BACKGROUND:

The vitamin D receptor (VDR) gene serves as a good candidate gene for susceptibility to several diseases. The gene has a critical role in regulating the renin-angiotensin system (RAS) influencing the regulation of blood pressure. Hence determining the association of VDR polymorphisms with essential hypertension is expected to help in the evaluation of risk for the condition.

AIM:

The aim of this study was to evaluate association between VDRFok I polymorphism and genetic susceptibility to essential hypertension.

MATERIALS AND METHODS:

Two hundred and eighty clinically diagnosed hypertensive patients and 200 normotensive healthy controls were analyzed for Fok I (T/C) [rs2228570] polymorphism by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) analysis. Genotype distribution and allele frequencies in patients and controls, and odds ratios (ORs) were calculated to predict the risk for developing hypertension by the individuals of different genotypes.

RESULTS:

The genotype distribution and allele frequencies of Fok I (T/C) [rs2228570] VDR polymorphism differed significantly between patients and controls (χ² of 18.0; 2 degrees of freedom; P = 0.000). FF genotype and allele F were at significantly greater risk for developing hypertension and the risk was elevated for both the sexes, cases with positive family history and habit of smoking.

CONCLUSIONS:

Our data suggest that VDR gene Fok I polymorphism is associated with the risk of developing essential hypertension     

Missense mutation G296S in GATA4 is not responsible for cardiac septal defects

BACKGROUND:

The most common type of congenital heart disease is the cardiac septal defects, which has reported to be caused by a missense mutation (G296S) in exon 3 of the GATA4 gene.

AIMS:

The present study was undertaken to find out whether GATA4 gene is the prime cause of the septal defects in Mysore population.

MATERIALS AND METHODS:

GATA4 gene analyses were undertaken on 21 confirmed CHD cases by PCR and DNA sequencing.

RESULTS AND CONCLUSION:

Analysis of this particular mutation in 21 septal defect patients revealed that none of the patients had the mutation, indicating that this mutation is population specific or septal defect in Mysore population is caused due to mutations in other regions of the GATA4 gene.     

Genetic and molecular analysis of the CLDN14 gene in Moroccan family with non-syndromic hearing loss

BACKGROUND:

Hearing loss is the most prevalent human genetic sensorineural defect. Mutations in the CLDN14 gene, encoding the tight junction claudin 14 protein expressed in the inner ear, have been shown to cause non-syndromic recessive hearing loss DFNB29.

AIM:

We describe a Moroccan SF7 family with non-syndromic hearing loss. We performed linkage analysis in this family and sequencing to identify the mutation causing deafness.

MATERIALS AND METHODS:

Genetic linkage analysis, suggested the involvement of CLDN14 and KCNE1 gene in deafness in this family. Mutation screening was performed using direct sequencing of the CLDN14 and KCNE1 coding exon gene.

RESULTS:

Our results show the presence of c.11C>T mutation in the CLDN14 gene. Transmission analysis of this mutation in the family showed that the three affected individuals are homozygous, whereas parents and three healthy individuals are heterozygous. This mutation induces a substitution of threonine to methionine at position 4.

CONCLUSION:

These data show that CLDN14 gene can be i mplicated in the development of hearing loss in SF7 family; however, the pathogenicity of c.11C>T mutation remains to be determined.     

Association of P213S polymorphism of the L-selectin gene with type 2 diabetes and insulin resistance in Chinese population

Aims

L-selectin belongs to selectin family of adhesion molecule and participates in the generation and development of type 2 diabetes (T2D). In this study, we evaluated the relationship between the P213S polymorphism of L-selectin gene and T2D and insulin resistance in the Chinese population.

Methods

We genotyped P213S polymorphism in 801 patients with T2D and 834 healthy controls in the Chinese population using polymerase chain reaction–ligase detection reaction (PCR–LDR) technique. Plasma glucose, insulin, lipid, blood urea nitrogen, creatinine and uric acid levels were measured by biochemical technique.

Results

The frequency of 213PP genotype and P allele of the L-selectin gene in patients with T2D was significantly higher than that in controls (P = 0.007; P = 0.019, respectively). The relative risk of allele P suffered from T2D was 1.191 times higher than that of allele S. Moreover, the levels of FPG and HOMA-IR of PP and PS genotype carriers were significantly higher than those of SS genotype carriers in the T2D group (P < 0.05).

Conclusion

These findings indicated that the P213S polymorphism of L‐selectin gene may contribute to susceptibility to T2D and insulin resistance in the Chinese population, and P allele appears to be a risk factor for T2D.     

Genetic polymorphisms of estrogen receptor alpha and catechol-O-methyltransferase genes in Turkish patients with familial prostate carcinoma

OBJECTIVES:

Estrogen is one of the most crucial hormones participating in the proliferation and carcinogenesis of the prostate glands. Genetic polymorphisms in the estrogen metabolism pathway might be involved in the risk of prostate carcinoma development. We evaluated the association between genetic polymorphisms in estrogen receptor alpha (ESR1) and catechol-O-methyltransferase (COMT) genes and the risk of developing familial prostate carcinoma.

MATERIALS AND METHODS:

In this study, 34 cases with prostate carcinoma whose first-degree relatives had prostate carcinoma and 30 healthy age-matched male controls were enrolled. The genotypes of ESR1 and COMT genes were analyzed employing polymerase chain reaction-restriction fragment length polymorphism method. 34 cases with prostate carcinoma, whose first degree relatives had prostate carcinoma and 14 age-matched male controls were enrolled to analyze the genotype of these two genes.

RESULTS:

Among control patients, the ESR1 PvuII genotypes of C/C, C/T and T/T were observed in 37%, 26% and 37%, respectively, whereas the C/C, C/T and T/T genotypes were observed in 18%, 41% and 41% of case patients, respectively. Among controls, the ESR1 PvuII allele frequencies of C and T were equally observed, whereas the C and T allele frequencies were observed in 38% and 62% of patients, respectively. Among ESR1 PvuII genotypes there were not any significant difference in terms of genotype (P = 0.199) and allele (P = 0.181) frequencies. Among controls, the ESR1 XbaI genotypes of G/G, G/A and A/A were observed in 33%, 37% and 33%, respectively, whereas the G/G, G/A and A/A genotypes were observed in 12%, 47% and 41% of patients, respectively. Among controls, the ESR1 XbaI allele frequencies of A and G were observed equally, respectively, whereas the A and G frequencies were observed in 65% and 35% of patients, respectively. Among ESR1 Χ baI, there was not any significant difference in terms of genotype (P = 0.111) and allele (P = 0.093) frequencies. But the C/C genotype of the PvuII site and G/G genotype of the XbaI site in the ESR1 gene were associated significantly with the risk of developing prostate carcinoma. The G/G, G/A and A/A genotypes of the COMT gene were observed in 50%, 29% and 21% of control patients and in 53%, 21% and 26% of case patients, respectively. The A and G allele frequencies of the COMT gene were observed in 36.7%, 63.3% of control patients and in 36.8%, 63.2% of case patients, respectively. In COMT gene, there was not any significant difference in terms of genotype (P = 0.843) and allele (P = 0.991) frequencies. But the G/A genotype of the COMT gene had a weak tendency toward increased risk.

CONCLUSION:

Polymorphisms of ESR1 gene in the estrogen metabolism pathway were associated significantly with familial prostate carcinoma risk. Single nucleotide polymorphisms of low-penetrance genes are targets for understanding the genetic susceptibility of familial prostate carcinoma.     

Population genetic evidence for speciation pattern and gene flow between Picea wilsonii,P. morrisonicola and P. neoveitchii

Background and Aims

Genetic drift due to geographical isolation, gene flow and mutation rates together make it difficult to determine the evolutionary relationships of present-day species. In this study, population genetic data were used to model and decipher interspecific relationships, speciation patterns and gene flow between three species of spruce with similar morphology, Picea wilsonii, P. neoveitchii and P. morrisonicola. Picea wilsonii and P. neoveitchii occur from central to north-west China, where they have overlapping distributions. Picea morrisonicola, however, is restricted solely to the island of Taiwan and is isolated from the other two species by a long distance.

Methods

Sequence variations were examined in 18 DNA fragments for 22 populations, including three fragments from the chloroplast (cp) genome, two from the mitochondrial (mt) genome and 13 from the nuclear genome.

Key Results

In both the cpDNA and the mtDNA, P. morrisonicola accumulated more species-specific mutations than the other two species. However, most nuclear haplotypes of P. morrisonicola were shared by P. wilsonii, or derived from the dominant haplotypes found in that species. Modelling of population genetic data supported the hypothesis that P. morrisonicola derived from P. wilsonii within the more recent past, most probably indicating progenitor–derivative speciation with a distinct bottleneck, although further gene flow from the progenitor to the derivative continued. In addition, the occurrence was detected of an obvious mtDNA introgression from P. neoveitchii to P. wilsonii despite their early divergence.

Conclusions

The extent of mutation, introgression and lineage sorting taking place during interspecific divergence and demographic changes in the three species had varied greatly between the three genomes. The findings highlight the complex evolutionary histories of these three Asian spruce species.     

Prevalence of methylenetetrahydrofolate reductase 677 C-T polymorphism among mothers of Down syndrome children

INTRODUCTION:

The relationship between chromosomal non-disjunction leading to aneuploidy and folate metabolism has drawn attention in the recent years. In this study, we examined the polymorphism in the gene encoding the folate metabolizing enzyme methylenetetrahydrofolate reductase (MTHFR), namely, 677 C-T in women having Down syndrome (DS) children.

MATERIALS AND METHODS:

The prevalence of these variant genotypes (MTHFR 677 C-T polymorphism) in women having DS children (case mothers) (n = 110) was compared with controls (n = 111) from Punjab. Genotyping was done using the polymerase chain reaction method followed by restriction fragment length polymorphism.

RESULTS:

In the present study, 1.8% of case mothers had TT genotype while none of the control mothers showed this genotype. T allele frequency among cases was 0.13 and 0.11 in controls. The Chi-square value showed a non-significant difference between cases and controls.

CONCLUSION:

No association has been observed between 677 C-T polymorphism and risk of non-disjunction in case mothers. Detection of polymorphisms in more genes of folate pathway is required to find out the exact cause of non-disjunction.     

THE +1245G/T POLYMORPHISMS IN THE COLLAGEN TYPE I ALPHA 1 (COL1A1) GENE IN POLISH SKIERS WITH ANTERIOR CRUCIATE LIGAMENT INJURY

Objectives

The aim of this study was to examine the association of +1245G/T polymorphisms in the COL1A1 gene with ACL ruptures in Polish male recreational skiers in a case-control study.

Methods

A total of 138 male recreational skiers with surgically diagnosed primary ACL ruptures, all of whom qualified for ligament reconstruction, were recruited for this study. The control group comprised 183 apparently healthy male skiers with a comparable level of exposure to ACL injury, none of whom had any self-reported history of ligament or tendon injury. DNA samples extracted from the oral epithelial cells were genotyped for the +1245G/T polymorphisms using real-time PCR method.

Results

Genotype distributions among cases and controls conformed to Hardy-Weinberg equilibrium (p = 0.2469 and p = 0.33, respectively). There was a significant difference in the genotype distribution between skiers and controls (p = 0.045, Fisher''s exact test). There was no statistical difference in allele distribution: OR 1.43 (0.91-2.25), p = 0.101 (two-sided Fisher''s exact test).

Conclusions

The risk of ACL ruptures was around 1.43 times lower in carriers of a minor allele G as compared to carriers of the allele T.     

Association of CYP3A5*3 polymorphism with development of acute leukemia

BACKGROUND:

CYP3A5 was observed to be an important genetic contributor to inter individual differences in CYP3A-dependent drug metabolism in acute leukemic patients. Loss of CYP3A5 expression was mainly conferred by a single nucleotide polymorphism at 6986A>G (CYP3A5*3). We investigated the association between CYP3A5*3 polymorphism and acute leukemia.

MATERIALS AND METHODS:

Two hundred and eighty nine acute leukemia cases comprising of 145 acute lymphocytic leukemia (ALL), 144 acute myeloid leukemia and 241 control samples were analyzed for CYP3A5*3 polymorphism using PCR-RFLP method. Statistical analysis was performed with SPSS version (15.0) to detect the association between CYP3A5*3 polymorphism and acute leukemia.

RESULTS:

The CYP3A5*3 polymorphism 3/3 genotype was significantly associated with acute leukemia development (χ²- 133.53; df-2, P 0.000). When the data was analyzed with respect to clinical variables, mean WBC, blast % and LDH levels were increased in both ALL and AML cases with 3/3 genotype. The epidemiological variables did not contribute to the genotype risk to develop either AML or ALL.

CONCLUSION:

The results suggest that the CYP3A5*3 polymorphism might confer the risk to develop ALL or AML emphasizing the significance of effective phase I detoxification in carcinogenesis. Association of the polymorphism with clinical variables indicate that the 3/3 genotype might also contribute to poorer survival of the patients.     

Single Nucleotide Polymorphism 8q24 rs13281615 and Risk of Breast Cancer: Meta-Analysis of More than 100,000 Cases

Background

The onset and progression of breast cancer (BC) is influenced by many factors, including the single nucleotide polymorphism (SNP) rs13281615 at 8q24. However, studies of the potential association between rs13281615 at 8q24 and risk of BC have given inconsistent results. We performed a meta-analysis to address this controversy.

Methods

PubMed, EMBASE and the Chinese National Knowledge Infrastructure databases were systematically searched to identify relevant studies. Two curators independently extracted data, and odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated to assess the strength of the association between rs13281615 at 8q24 and risk of BC.

Results

Fourteen studies are included in the meta-analysis, involving 44,283 cases (5,170 Chinese and 39,113 mixed) and 55,756 controls (5,589 Chinese and 50,167 mixed). The GG and G-allele genotypes of rs13281615 at 8q24 are significantly associated with increased risk of BC (GG vs. AG+AA, OR 1.13, 95% CI 1.08–1.19, P<0.001; G-allele vs. A-allele, OR 1.10, 95% CI 1.06–1.14, P<0.001; GG vs. AA, OR 1.20, 95% CI 1.12–1.29, P<0.001). Conversely, the AA genotype is significantly associated with decreased risk of BC (AA vs. AG+GG, OR 0.89, 95% CI 0.84–0.93, P<0.001).

Conclusion

G-allele genotypes of rs13281615 at 8q24 polymorphism are a risk factor for developing BC, while the AA genotype is a protective factor. Further large and well-designed studies are required to confirm this conclusion.