LINKS BETWEEN RENIN-ANGIOTENSIN SYSTEM GENETIC POLYMORPHISMS AND LEPTIN SECRETION IN OBESE HEART FAILURE PATIENTS.

Chronic heart failure (CHF) and obesity are two conditions frequently associated and which, despite all the advances made in their management in the recent years, their prevalence continues to rise. Obese patients present unique challenges in the diagnosis of CHF and also therapeutic particularities. The genetic differences may be a possible explanation for the fact that some people, irrespective of their lifestyle and common classical cardiovascular risk factors, are more susceptible to develop heart failure. Moreover, the adipose tissue, a huge endocrine organ which secretes adipokines, is also a well-established source of all renin-angiotensin-aldosterone system components, being strongly involved in the pathogenesis of CHF. That is why this review will explore the possible links between the RAS genetic polymorphisms and leptin secretion in obese HF patients, trying to bring a more precise understanding of this relationship, which will undoubtedly facilitate a more appropriate treatment of HF in obese patients. We also try to explain the possible incriminated mechanisms, and plausible biological explanations for the relationship between RAS genetic polymorphisms and adipokines secretion in obese heart failure patients.

Newborn LpL (Ser447Stop, Asn291Ser) genotypes and the interaction with maternal genotypes influence the risk for different types of preeclampsia: modulating effect on lipid profile and pregnancy outcome.

AIM: To establish that newborn Ser447Stop and Asn291Ser may have interactive effects with maternal genotypes on the plasma lipoprotein levels, risk of preeclampsia as well as on the prognosis of preeclampsia. MATERIALS AND METHODS: Seventy preeclamptic women and 94 normotensive pregnant women, and their newborns were genotyped using PCR-RFLP methods. RESULTS: The risk of mild and severe preeclampsia was 4 (p = 0.004) and 5.18 (p = 0.001), respectively, if both the mother and newborn were carriers of the Ser447/Ser477 genotype. If both the mother and newborn were carriers of the Asn291Ser variant, the risk to develop severe preeclampsia was 6.07 (p = 0.03). Women with mild and severe preeclampsia had higher TG (p < 0.001; p < 0.001) and LDL-C levels (p = 0.008; p < 0.001) if both the mother and newborn were carriers of the Ser447/Ser447 genotype. Women with severe preeclampsia had significantly higher TG (p = 0.03) and LDL-C levels (p = 0.037) if both the mother and newborn were carriers of Asn291Ser. Newborn/maternal LpL interaction had no statistically significant influence on pregnancy outcome. CONCLUSIONS: The newborn/maternal LpL interaction influences the severity of preeclampsia and modulates the lipid profile particularly in severe preeclampsia.

Lys751Gln XPD and Arg399Gln XRCC1 in Romanians. Association with sporadic colorectal cancer risk and different stages of carcinomas.

BACKGROUND: DNA repair processes involved the removal of modified bases through the base excision repair (BER) pathway and removal of damaged nucleotides through the nucleotide excision repair (NER) pathways. METHODS: in order to determine the association between XPD(Lys751Gln) and XRCC1 (Arg399Gln) SNPs and the risk of CRC as well as tumor grade and stages in Romanians we genotyped using PCR-RFLP methods 150 patients (80 females and 70 males) and 162 controls (100 females and 62 males). RESULTS: The risk (odds ratio - OR) to develop sporadic CRC was 3.02 (p=0.02) and 3.49 (p=0.001), respectively, in association with the homozygous Gln751 Gln751-XPD and Gln399 Gln399-XRCC1 genotypes. Higher risk for carriers of the Gln751 Gln751 - Arg399 Arg399 (OR 4.19, p=0.027),Gln399 Gln399 - Lys751 Lys751 (OR 3.21, p=0.013),Gln399 Gln399 - Lys751 Gln751 (OR 4.5, p=0.05),Lys751 Gln751 - Arg399 Gln399 (OR 3.94, p 0.001) combined genotypes was observed. The lowest risk was observed in carriers of Lys751 Lys751-Arg399 Arg399 genotypes (OR0.24, p 0.001). 2.24-fold (p=0.05) and 3.75-fold (p=0.004)increased risk (OR) for carriers of the Lys751Gln or Arg399Gln variants to be on stage pT2 and pT4, respectively. Patients carriers of Lys751Gln or Arg399Gln variants had 7.7-fold(p=0.002) and 18.94-fold (p 0.001) increased risk (OR) to develop sporadic CRC in stage D. CONCLUSIONS: XPD and XRCC1 variants affect the risk for sporadic CRC in Romanians, seem to be associated with more aggressive forms of sporadic CRC and may be prognostic factors in patients with advanced CRC.

The effect of the D1-C785T polymorphism in the type 1 iodothyronine deiodinase gene on the circulating thyroid hormone levels in Romanian women with preeclampsia. Association with the degree of severity and pregnancy outcome of preeclampsia.

AIM: To investigate the biochemical and genetic thyroid status in women with preeclampsia by the determination of serum FT3 and FT4 levels in association with D1-C785T genotypes. METHODS: We genotyped using PCR-RFLP methods 50 women with preeclampsia and 50 normotensive pregnant women. RESULTS: FT3 levels (pg/ml, 2.63 ± 0.56 vs. 2.91 ± 1.41) were low, and FT4 levels (ng/dl, 1.11 ± 0.3 vs. 0.88 ± 0.14) were high in women with preeclampsia compared to normal pregnant women. The association with severe preeclampsia was stronger for the homozygous T/T genotype (OR 6.57, p = 0.029). Women with preeclampsia with the D1-T785 mutated allele had lower FT3 levels (pg/ml, 2.31 ± 0.81 vs. 3.04 ± 0.39, p < 0.001), higher FT4 levels (ng/dl, 1.32 ± 0.87 vs. 0.84 ± 0.24, p = 0.009) than women with preeclampsia with the D1-C/C genotype. Significant decrease in serum FT3 levels in positive women with severe preeclampsia compared to women negative for this genetic variation (pg/ml, 1.59 ± 0.74 vs. 2.77 ± 0.23, p = 0.003) was observed. Women with severe preeclampsia, positive for the mutated T785 allele, delivered at a significantly lower gestational age (31.75 ± 3.69 vs. 38.66 ± 3.21 weeks, p = 0.035) neonates with a lower birth weight (1861.11 ± 869.9 vs. 3500 ± 424.26 g, p = 0.023) compared to women negative for the same allele. CONCLUSIONS: Thyroid hormone levels and the D1-C785T polymorphism, alone or in combination, correlate with the severity of preeclampsia. The D1-C785T polymorphism influences the outcome of pregnancy in severe preeclampsia.

[Correlation between C677T and A1298C mutations of the MTHFR gene and therapeutic prognostic elements in colorectal cancer]. / Relatia mutatiilor C677T si A1298C ale genei MTHFR cu elemente de prognostic terapeutic in cancerul colorectal.

The MTHFR gene polymorphism may influence the risk of developing sporadic CRC. The aim of this study is to assess the relationship between the mutations of this gene and certain aspects of the surgical practice: the tumoral resectability, the tumoral recurrence and the disease-free interval. 69 patients with sporadic colorectal cancer that underwent surgery at the 3rd Surgery Department of Cluj-Napoca between October 2003-May 2005 were randomly selected. The correlations between the C677T, A1298C mutations and the prognostic factors mentioned above were analyzed. The results show that the C677T mutation increases the risk of non-resectability (OR = 3.5, p = 0.099), while the A1298C mutation does not (OR = 1.1). For the A1298C mutation there is a major risk of recurrence (OR = 3,063), but in the group with C677T mutation there is only a small increase of the risk, non-significant statistically (OR = 1,196). Both the groups with the C677T mutation and the "wild" genotype 1298AA have more precocious recurrences then the other groups, so a shorter disease-free interval (HR = 0.9458 respectively 3.1070). The patients with the A1298C mutations have more often non-resectable recurrences. In conclusion, the mutations of the MTHFR gene are a prognostic factor for the treatment and evolution of patients with CRC.

G20210A prothrombin gene mutation identified in patients with venous leg ulcers.

The G20210A mutation variant of prothrombin gene is the second most frequent mutation identified in patients with deep venous thrombosis, after factor V Leiden. The risk for developing deep venous thrombosis is high in patients identified as heterozygous for G20210A mutation. In order to identify this polymorphism in the gene coding prothrombin, the 345bp fragment in the 3'- untranslated region of the prothrombin gene was amplified using amplification by polymerase chain reaction and enzymatic digestion by HindIII (restriction endonuclease enzyme). The products of amplification and enzymatic's digestion were analized using agarose gel electrophoresis. We investigated 20 patients with venous leg ulcers and we found 2 heterozygous (10%) for G20210A mutation. None of the patients in the control group had G20210A mutation. Our study confirms the presence of G20210A mutation in the Romanian population. Our study also shows the link between venous leg ulcers and this polymorphism in the prothrombin gene.