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Background/Purpose Autosomal dominant hypercholesterolemia (ADH) is an autosomal dominant inherited disease characterized by an increase in low-density lipoprotein cholesterol levels and premature coronary heart disease, which can be caused by mutations in genes encoding the low-density lipoprotein receptor ( LDLR ), apolipoprotein B ( APOB ) and proprotein convertase subtilisin/kexin type 9 ( PCSK9 ). There is scant information with regard to the role played by each gene in the Taiwanese ADH population, especially the newly discovered PCSK9 gene. Methods We used coupling heteroduplex analysis based on a denaturing high performance liquid chromatography system and DNA sequencing to screen for the LDLR gene, APOB gene and PCSK9 gene in 87 ADH cases recruited from 30 unrelated Taiwanese families. Results We did not find any mutation-causing variant of the PCSK9 gene in our cases and thus excluded PCSK9 as the major culprit mutation in these families. On the other hand, we identified six previously reported LDLR gene mutations (C107Y, D69N, R385W, W462X, G170X, V408M), two novel LDLR gene mutations (FsG631 and splice junction mutation of intron 10), and one known mutation (R3500W) and one novel missense mutation (T3540M) in the APOB gene that were present in 55 members from 18 ADH families (60%). R3500W, rather than R3500Q, could be the principle mutation responsible for familial defective apolipoprotein B in Taiwanese. Conclusion The results of our study reveal a characteristic mutation pattern of ADH in Taiwan, mainly in the LDLR and APOB genes. However, PCSK9 gene mutation may not be a major cause of ADH in our study population.

Amphiregulin (AR), an epidermal growth factor (EGF)-like molecule, is a mitogen for keratinocytes. Squamous cell carcinoma (SCC) is a tumor derived from keratinoctyes. Expression of AR mRNA positively correlated with the clinical progression of 39 oral SCC. Oral SCC line, KB, was used as a model to study if increased expression of AR altered the biological behaviors of SCC cells. Exogenous AR dose-dependently enhanced the proliferation of KB cells expressing EGF receptor 1 (EGFR-1), a major receptor for AR, but little AR. Neutralizing anti-AR antibody significantly reversed the stimulatory effect of exogenous AR on KB cell proliferation. Ectopically expressed AR in stable clones manifested higher abilities to proliferate, migrate and invade Matrigel than vector control. Cyclooxygenase 2 (COX-2), but not metalloprotease 9 (MMP-9) mRNA, was increased in all the AR-expressing stable clones. In summary, AR behaves as a tumor promoter for oral SCC cells partly via increased expression of COX-2.

193 Sir, As the authors of the article “LDLR and ApoB are Major Genetic Causes of Autosomal Dominant Hypercholesterolemia in a Taiwanese Population” in the October 2007 issue of the Journal of the Formosan Medical Association,1 we found two numbering errors regarding the novel polymorphisms of the LDLR gene we identified in patients with autosomal dominant hypercholesterolemia. In Table 4, the two novel polymorphisms of the LDLR gene were originally numbered as A G1415 in exon 10 and C T2258 in exon 16. However, these numbers are erroneous and they should be relabeled as A G1374 (exon 10, Arg >Arg) and C T2358 (exon 16, Ser>Ser), respectively. The text describing the LDLR gene variants in the results section (page 803, lines 17–18 under the LDLR gene variants subheading) should also be corrected to “A>G at 1374 and C>T at 2358”). Both of the polymorphisms were confirmed by screening 50 control DNA samples (100 alleles) and cross-matching in the LDLR mutation database.2 As the information is important to the understanding of autosomal dominant hypercholesterolemia in Taiwanese people, and as the polymorphisms could also be incorporated into LDLR mutation databases, we hereby write in to formally correct our article. We thank Professor Anne K. Soutar from the Lipoprotein Group of the MRC Clinical Sciences Center in Imperial College London for the discussion of our data.