Abstract

Hyperhomocysteinemia is a known risk factor for thrombosis in both adults and children. Mutations of genes encoding the enzymes in homocysteine metabolism are predicted to cause elevation of homocysteine and increase the risk of thrombosis. Therefore, this study objectives are to determine the prevalence of methylenetetrahydrofolate reductase (MTHFR) 677C->T, 1298A->C; methionine synthase (MS) 2756A->G, and cystathione β-synthase (CBS) 884ins68 in Thai ethnic patients, aged ≤18 years, and their relationship to thrombosis. The population consisted of 91 patients, from 2 medical institutes in Thailand, first diagnosed with thrombosis. The control group was 169 healthy, Thai children matched for age (mean ± SD in cases/controls = 9.4 ± 5.7 / 9.3 ± 5.7 years, p = 0.9) and sex (male/female in cases/controls = 57.1%/42.9%/53.8%/46.2%, p = 0.7). Genotyping was performed using standard PCR/restriction enzyme assays. The prevalence and allele frequency of the genes are shown in Table 1. The polymorphisms of individual genes and the combinations between the genotype did not affect plasma homocysteine level. The details are shown in Table 2. Conclusion, the prevalence of MTHFR 677C->T, 1298A->C, MS 2756A->G, and CBS 884ins68 in Thai population was lower than Caucasian population; and did not cause the increase risk for thrombosis in Thai children.

Table 1.

Frequency of genetic polymorphisms between patients and controls.

MTHFR 677ACC (%)CT (%)TT (%)T frequency (%)
Controls 71.8 27 1.2 14.7 
Patients 73.5 25.3 1.2 
p-value 0.91 0.96 
MTHFR 1298 AA (%) AC (%) CC (%) C frequency (%) 
Controls 50.0 42.1 7.9 24.4 
Patients 54.3 42.0 3.7 
p-value 0.76 0.26 
MS 2756 AA (%) AG (%) GG (%) G frequency (%) 
Controls 78.9 21.1 10.5 
Patients 75.9 24.1 
p-value 0.63 
CBS 884ins68 NN (%) NI (%) II (%) G frequency (%) 
Controls 98.7 0.6 0.6 
Patients 98.7 1.3 
p-value 0.55 
MTHFR 677ACC (%)CT (%)TT (%)T frequency (%)
Controls 71.8 27 1.2 14.7 
Patients 73.5 25.3 1.2 
p-value 0.91 0.96 
MTHFR 1298 AA (%) AC (%) CC (%) C frequency (%) 
Controls 50.0 42.1 7.9 24.4 
Patients 54.3 42.0 3.7 
p-value 0.76 0.26 
MS 2756 AA (%) AG (%) GG (%) G frequency (%) 
Controls 78.9 21.1 10.5 
Patients 75.9 24.1 
p-value 0.63 
CBS 884ins68 NN (%) NI (%) II (%) G frequency (%) 
Controls 98.7 0.6 0.6 
Patients 98.7 1.3 
p-value 0.55 
Table 2.

Homocysteine value and genetic polymorphisms.

Genetic polymorphism (number)Plasma Hcy (μmol/L)p value
MTHFR 677 
CC (n=105) 7.4 ± 2.9 0.11 
CT (n=29) 8.3 ± 2.7  
MTHFR 1298 
AA (n=64) 7.4 ± 2.4 > 0.05 
AC (n=59) 7.5 ± 2.8 > 0.05 
CC (n=12) 8.7 ± 5  
MS 2756 
AA (n=110) 7.8 ± 3  
AG (n=25) 6.7 ± 1.9 0.055 
CBS 884 ins 68 
DD (n=137) 7.5 ± 2.8  
ID (n=2) 10.3 ± 8.7 0.72 
MTHFR 677 / MTHFR 1298 
CT/AC (n=16) 8.7 ± 2.5 0.07 
MTHFR 1298 / MS 2765 
AC/AG (n=6)6.8 ± 1.6 6.8 ± 1.6 0.38 
MTHFR 1298 / CBS884ins68 
AC/IN (n=9) 6.8 ± 2.1 0.34 
Genetic polymorphism (number)Plasma Hcy (μmol/L)p value
MTHFR 677 
CC (n=105) 7.4 ± 2.9 0.11 
CT (n=29) 8.3 ± 2.7  
MTHFR 1298 
AA (n=64) 7.4 ± 2.4 > 0.05 
AC (n=59) 7.5 ± 2.8 > 0.05 
CC (n=12) 8.7 ± 5  
MS 2756 
AA (n=110) 7.8 ± 3  
AG (n=25) 6.7 ± 1.9 0.055 
CBS 884 ins 68 
DD (n=137) 7.5 ± 2.8  
ID (n=2) 10.3 ± 8.7 0.72 
MTHFR 677 / MTHFR 1298 
CT/AC (n=16) 8.7 ± 2.5 0.07 
MTHFR 1298 / MS 2765 
AC/AG (n=6)6.8 ± 1.6 6.8 ± 1.6 0.38 
MTHFR 1298 / CBS884ins68 
AC/IN (n=9) 6.8 ± 2.1 0.34 

Disclosure: No relevant conflicts of interest to declare.

Author notes

*

Corresponding author