The third locus was rs12108602 closed to NDST4 at 4q26 which showed significant results in both COGA (p=4.32×10−4) and SAGE (p=6.24×10−5) samples. In addition, two of the SNPs have been replicated in the OZALC sample (rs2620418 with p = 0.0103 and rs11938588 with p = 0.0203). rs11938588 has significant cis-acting regulatory effect on NDST4 transcript expression. NDST4 whose alias as N-deacetylase/N-sulfotransferase (heparan glucosaminyl) 4 has weak deacetylase activity but high sulfotransferase. It has clear differences in distribution and enzymatic properties. Different combinations of the isozymes may account for some of the differences seen in heparan sulfates from various tissues (Aikawa et al., 2001). Previous genome linkage study identified chromosome 4 in the vicinity of the alcohol dehydrogenase (ADH) gene cluster (Saccone et al., 2000) while additional analyses of chromosome 4 showed modest evidence for both linkage and association. Recently, SNP rs7671475 in NDST4 showed a borderline association with AD (Kalsi et al., 2010).
