[1853] Association between Methylenetetrahydrofolate Reductase (MTHFR) Gene Variants and Hyperhomocysteinemia in United States Veterans

Mohammad M Pessarakli, Ryan T Phan. Keck School of Medicine of USC, Los Angeles, CA; Veterans Affairs of Greater Los Angeles Healthcare System, Los Angeles, CA; David Geffen School of Medicine of UCLA, Los Angeles, CA

Background: The MTHFR gene encodes 5,10-methylenetetrahydrofolate reductase (MTHFR), which regulates homocysteine metabolism. MTHFR gene variants such as C677T and A1298C may predispose to hyperhomocysteinemia - a risk factor for cardiovascular disease and arterial and venous thrombosis. Existing evidence for the relationship between MTHFR and hyperhomocysteinemia is, however, conflicting. This study investigates the association between MTHFR gene variants and hyperhomocysteinemia in a cohort of US veterans at the VA hospital in Los Angeles.
Design: This study is ongoing and includes 120 randomly selected cases from 01/2011-08/2012. Homocysteine level above 13.9 µmol/L is considered elevated. MTHFR is genotyped by the eSensor platform and recorded for C677T variant as: CC (WT), CT (Het), TT (Hom); A1298C variant as: AA (WT), AV (Het), VV (Hom).
Results: 36 (30%) of 120 cases met selection criteria. Age range of patients is 31 to 90 years. Table 1 reports the MTHFR genotypes of the study population.

Table 1
MTHFRCCAACTAATTAACCAVCTAVCCVV
No. (%)9 (25)10 (28)4 (11)7 (19)5 (14)1 (3)
Age (avg.)63.555.356.7560.764.665
Female1(50)001(50)00
Male8(23.5)10(29.4)4(11.8)6(17.6)5(14.7)1(2.9)
Black6(46.2)1(7.7)05(38.5)01(7.7)
Caucasian1(7.7)5(38.5)2(15.4)2(15.4)3(23)0
Hispanic01(100)0000
Other2(22.2)3(33.3)2(22.2)02(22.2)0


15 (41.7%) of the 36 patients have elevated homocysteine. No association is observed between MTHFR C677T or A1298C and homocysteine level. The mean/median homocysteine levels among C677T genotype are CC(12.48/11.80), CT(14.4/13.14), TT(12.86/12.82); among A1298C are AA(13.19/12.56), AV(13.54/12.07), VV(16.19/16.19). Mean/median homocysteine levels for combined variants are shown in Table 2.

Table 2
MTHFRCCAACTAATTAACCAVCTAVCCVV
Median11.8213.0012.8211.7813.2716.19
Mean12.9513.5812.8611.8715.8916.19



Conclusions: No association is found between MTHFR variants C677T or A1298C and elevated homocysteine. Compound heterozygous C677T/A1298C or homozygous C677T and hyperhomocysteinemia are also not correlated. The findings suggest that MTHFR variants are not reliable predictors of hyperhomocysteinemia among the US Veteran population. Additional data is expected at the USCAP Annual Meeting.
Category: Pathobiology

Monday, March 4, 2013 9:30 AM

Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 281, Monday Morning

 

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