Maria Clara Bicho

The Role of Haptoglobin and Its Genetic Polymorphism in Cancer: A Review

Acute phase response is a stereotyped innate nonspecific reaction of the body proceeding specific immune reactions. It ́s a systemic homeostatic reaction of the organism to local and or systemic disturbances caused by infections, tissue injury, trauma, immunologic disorders and neoplasias (Ron D et al 1990, Trautwein C et al 1994, Gruys E et al 2005). Proinflammatory cytokines are released at the place of tissue injury, diffuses locally and systemically to the vascular system and activates receptors on different target cells resulting in the activation of hypothalamic-pituitary-adrenal axis (HPAA), results in the production of growth hormone secretion and induces changes in the concentration of several plasma proteins (Ron D et al 1990, Trautwein C et al 1994, Gruys E et al 2005).

In Women with Previous Pregnancy Hypertension, Levels of Cardiovascular Risk Biomarkers May Be Modulated by Haptoglobin Polymorphism

Preeclampsia (PE) may affect the risk for future cardiovascular disease. Haptoglobin (Hp), an acute phase protein with functional genetic polymorphism, synthesized in the hepatocyte and in many peripheral tissues secondary of oxidative stress of PE, may modulate that risk through the antioxidant, angiogenic, and anti-inflammatory differential effects of their genotypes. We performed a prospective study in 352 women aged 35 ± 5.48 years, which 165 had previous PE, 2 to 16 years ago. We studied demographic, anthropometric, and haemodynamic biomarkers such as C-reactive protein (CRP), myeloperoxidase (MPO), and nitric oxide metabolites (total and nitrites), and others associated with liver function (AST and ALT) and lipid profile (total LDL and cholesterol HDL, non-HDL, and apolipoproteins A and B). Finally, we study the influence of Hp genetic polymorphism on all these biomarkers and as a predisposing factor for PE and its remote cardiovascular disease prognosis. Previously preeclamptic women either hypertensive or normotensive presented significant differences in those risk biomarkers (MPO, nitrites, and ALT), whose variation may be modulated by Hp 1/2 functional genetic polymorphism. The history of PE may be relevant, in association with these biomarkers to the cardiovascular risk in premenopausal women.

Epistatic Interaction of CYP1A1 and COMT Polymorphisms in Cervical Cancer

There is a clear association between the excessive and cumulative exposure to estrogens and the development of cancer in hormone-sensitive tissues, such as the cervix. We studied the association of CYP1A1 M1 (rs4646903) and COMT (rs4680) polymorphisms in 130 cervical cancer cases (c-cancer) and 179 controls. The CYP1A1 TT genotype was associated with a lower risk for c-cancer (OR = 0.39, p = 0.002). The allele C of CYP1A1 was a risk for c-cancer (OR = 2.29, p = 0.002). Women with COMT LL genotype had a higher risk of developing c-cancer (OR = 4.83, p < 0.001). For the interaction of the CYP1A1&COMT, we observed that TC&HL genotypes had a greater risk for c-cancer (OR = 6.07, p = 0.006) and TT&HL genotypes had a protection effect (OR = 0.24, p < 0.001). The CYP1A1 TT and COMT LL genotypes had higher estradiol levels in c-cancer (p < 0.001 and p = 0.037, resp.). C-cancer is associated with less production of 2-methoxy-estradiol resultant of functional polymorphisms of CYP1A1 and COMT, separately. CYP1A1 and COMT work in a metabolic sequence and their interaction could lead to an alternative pathway of estrogen metabolism with production of 16-OH-estrone that is more proliferative.

PP004. The polymorphism C677T of methylenetetrahydrofolate reductase (MTHFR), may increase risk for future higher blood pressure in women with previous hypertension in pregnancy

INTRODUCTION The MTHFR is a key enzyme in the folate cycle involved in homocysteine remethylation. The T allele of MTHFR C677T polymorphism is associated with lower activity inhibiting the DNA methylation and protecting from oxidative stress. OBJECTIVES To evaluate the MTHFR genotype-phenotype relationship during and after pregnancy comparing hypertensive with normotensive women. METHOD A sample of 380 women with 32.54±6.478 years old, 181 normotensive (NT) and 199 hypertensive (HBP) being 70.3% above 34 weeks of gestation. A subgroup 63 women with history of preeclampsia were studied 3-6 years postpartum and compared with 59 controls. The MTHFR was evaluated by PCR-RFLP using DNA extracted from peripheral blood. Statistical analysis evaluated with appropriated tests. RESULTS The distribution of genotypes of the MTHFR was different according to blood pressure (BP), it was observed that the TT genotype had lower frequency in HBP (p<0.001). In the subgroup CC+CT the MPO levels were higher in HBP as well as nitrites, leucocytes, neutrophils, Apo B, BMI, waist and ratio waist/hip compared with NT (p<0.001, p=0.04, p=0.042, p=0.035, p=0.03, p=0.022, p=0.026, respectively). There were differences between levels of BP systolic and diastolic between women previously HBP and NT of CC+CT compared with TT carriers (p<0.001). CONCLUSION The MTHFR may modulate blood pressure (BP) and cardiovascular risk. TT genotype with increased expression of antioxidant enzymes, may be a protective factor for future hypertension and cardiovascular risk compared with women CC and CT genotypes with higher levels of circulating biomarkers of inflammation.