Glutamate carboxypeptidase II (<i style="mso-bidi-font-style:normal">GCPII</i>) genetic variants as determinants of hyperhomocysteinemia: Implications in stroke susceptibility
356-362<span style="mso-bidi-font-size:9.0pt;letter-spacing:
-.1pt" lang="EN-GB">The rationale of this case-control study is to ascertain whether
glutamate carboxypeptidase II (GCPII) variants serve as determinants of
hyperhomocysteinemia and contribute to the etiology of stroke.
Hyperhomocysteinemia was observed in stroke cases compared to controls (14.09 ±
7.62 <span style="mso-bidi-font-size:9.0pt;font-family:Symbol;
mso-ascii-font-family:" times="" new="" roman";mso-hansi-font-family:"times="" roman";="" letter-spacing:-.1pt;mso-char-type:symbol;mso-symbol-font-family:symbol"="" lang="EN-GB">mmol/L vs. 8.71
± 4.35, P GCPII sequencing revealed two known
variants (R190W and H475Y) and six novel variants (V108A, P160S, Y176H, G206R,
G245S and D520E). Among the haplotypes of GCPII,
all wild-haplotype H0 showed independent association with stroke risk (OR:
9.89, 95% CI: 4.13-23.68), while H2 representing P160S variant showed reduced
risk (OR: 0.17, 95% CI: 0.06-0.50). When compared to subjects with H2
haplotype, H0 haplotype showed elevated homocysteine levels (18.26 ± 4.31 <span style="mso-bidi-font-size:9.0pt;font-family:Symbol;mso-ascii-font-family:
" times="" new="" roman";mso-hansi-font-family:"times="" roman";letter-spacing:-.1pt;="" mso-char-type:symbol;mso-symbol-font-family:symbol"="" lang="EN-GB">mmol/L vs. 13.66 ± 3.72 <span style="mso-bidi-font-size:9.0pt;font-family:Symbol;mso-ascii-font-family:
" times="" new="" roman";mso-hansi-font-family:"times="" roman";letter-spacing:-.1pt;="" mso-char-type:symbol;mso-symbol-font-family:symbol"="" lang="EN-GB">mmol/L, P = 0.002) and reduced plasma folate
levels (<span style="mso-bidi-font-size:9.0pt;letter-spacing:
-.1pt;mso-ansi-language:EN-US" lang="EN-US">7.09 ± 1.19 ng/ml vs. 8.21 ± 1.14 ng/ml, P = 0.007). Using GCPII genetic variants, dietary folate
and gender as predictor variables and homocysteine as outcome variable, a
multiple linear regression model was developed. This model explained 36%
variability in plasma homocysteine levels. To conclude, GCPII haplotypes
influenced susceptibility to stroke by influencing homocysteine levels.
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