ABSTRACT
Hyperuricemia is related to metabolic syndrome, and is defined as an over-production or under-excretion of uric acid (UA), with increased UA serum concentration. Among other causes, Hyper-homocysteinemia (H-Hcy) can be responsible for hyperuricemia. The mechanisms underlying the association between these two conditions are unclear, but increased UA serum levels can be a consequence of renovascular atherosclerosis, with reduced UA excretion. An alternative hypothesis is the over-production of UA from adenosine (originating from S-adenosyl-homocysteine). Genetic polymorphism (C677T) of methylenetetrahydrofolate reductase (MTHFR) may contribute. A possible mechanism is purines biosyinthesis originating from this gene variant. However, the results obtained from several studies and meta-analyses of the relationship between H-Hcy and hyperuricemia are ambivalent, and broader research is needed.
Subject(s)
Adenosine , Atherosclerosis , Homocysteine , Hyperuricemia , Methylenetetrahydrofolate Reductase (NADPH2) , Polymorphism, Genetic , Purines , Uric AcidABSTRACT
Los defectos del tubo neural (DTN) son las alteraciones congénitas más frecuentes del sistema nervioso central. El mecanismo de transmisión hereditario de los DTN aislados es multifactorial, se debe a la interacción de factores ambientales y genéticos. El polimorfismo 677C>T del gen de la metilentetrahidrofolato reductasa (MTHFR) ha sido implicado como factor de riesgo para DTN. El objetivo de este trabajo fue investigar la asociación del polimorfismo 677C>T del gen de la MTHFR como factor de riesgo en los DTN. Se analizaron muestras de ADN de 52 madres con antecedente de al menos un hijo con DTN y de 119 madres controles. A través de la reacción en cadena de la polimerasa se amplificó un fragmento de 198 pb, el cual se sometió a digestión con la enzima HinfI. La frecuencia alélica de la MTHFR en los grupos problema y control fue de 51,92% y 34,45%; para el alelo T y 48,08% y 65,55%; para el C respectivamente. Se encontró diferencia significativa entre las frecuencias del alelo T y del alelo C (p: 0,002), así como entre las frecuencias genotípicas (p: 0,007) al ser comparadas en ambos grupos. El odds ratio (OR) para el genotipo TT vs CC se estimó como OR: 4,9 [IC 95%: 1,347-6,416] p: 0,002; CT+TT vs CC: OR: 2,9 [IC 95%: 1,347-6,416] p: 0,005; TT vs CT+CC: OR: 2,675 [IC 95%: 1,111-6,441] p: 0,024. Los presentes datos aportan una asociación significativa entre el polimorfismo 677C>T de la MTHFR y riesgo aumentado en las madres con antecedente de hijos con DTN.
Neural tube defects (NTD) are the most common congenital anomalies of the central nervous system, with a multifactorial pattern of inheritance, presumably involving the interaction of several genetic and environmental factors. The methylenetetrahydrofolate reductase (MTHFR) gene 677C>T polymorphism has been implicated as a risk factor for NTD. The main objective of this research was to investigate the association of the 677C>T polymorphism of the MTHFR gene as a genetic risk factor for NTD. Molecular analysis was performed in DNA samples from 52 mothers with antecedent of NTD offspring and from 119 healthy control mothers. Using the Polymerase Chain Reaction, a 198 bases pairs fragment was digested with the restriction enzyme HinfI. 677T MTHFR allele frequencies for the problem and the control groups were 51.92% and 34.45%, respectively, and 677C MTHFR allele frequencies were 48.08% and 65.55%, respectively. There were significant differences in allele (p: 0.002) and genotype (p: 0.007) frequencies between these two groups. The odds ratio (OR) to the TT genotype vs the CC genotype was estimated as OR: 4.9 [95% CI: 1,347-6.416] p: 0.002; CT+TT vs CC: OR: 2.9 [95% CI: 1.347-6.416] p: 0.005; TT vs CT+CC: OR: 2.675 [95% CI: 1,111-6.441] p: 0.024. The data presented in this study support the relationship between MTHFR 677C>T polymorphism and risk in mothers with antecedent of NTD offspring.