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研究者发现，第7染色体的一种基因变化，可能与偶发的肌萎缩性脊髓侧索硬化症（amyotrophic lateral sclerosis，ALS）之可能性强烈有关；这篇整组基因（Genome-Wide）研究，线上发表于12月16日的Nature Genetics期刊，辨识了DPP6的变化，此一基因已知可以在老鼠往下调节50%以上的脊索损伤。
ALS一般被称为葛雷克氏症(Lou Gehrig's disease)，是一种渐进式的破坏、往往致命之运动神经元损坏的神经异常，有10%的ALS案例是遗传性的，与数个基因的突变有关，其他的90%是偶发性的；稍早的报告指出ALS与基因变化之间的关联，但是这些变化在其他族群上并不一定适用。
这篇新的研究是首度辨识一大群样本的ALS与基因变化的研究(共有1767位ALS病患，1916位对照组)，这些研究对象分别来自荷兰、美国、瑞典和比利时，分析发现，整组基因中仅有1种单核苷酸多态性（Single Nucleotide Polymorphism，SNP）—位于DPP6的SNP (整体P = 5.04 × 10?8)；相较于1个对偶子 (OR, 1.20; 95% CI = 1.06 – 1.41)，带有2个对偶子的ALS风险可能性更高 (风险比 [OR], 1.60; 95%信心区间[CI] = 1.32 – 1.92)。
报告的结论为，辨识DPP6的常见变化是偶发ALS基因研究令人振奋的第一步。
共同作者、荷兰Utrecht大学医学中心基因医学系、加州大学洛杉矶分校精神神经研究中心的Roel A. Ophoff博士以电子邮件向Medscape病理学表示，我们是首度提出偶发ALS与基因之间关联的研究，且有统计上的证据，这表示我们首度提出了一个新的中心点，点出了此病症病理学的新研究方向。
不过，Ophoff博士表示，这不表示已经有可以上手的治疗方式，因为我们只发现1个基因，未来还有许多路要走。
Nat Genet. 线上发表于2007年12月16日。
Gene Variant Increases Susceptibility to Amyotrophic Lateral Sclerosis
By Jacquelyn K. Beals, PhD, PhD
Medscape Medical News
Investigators have found that a gene variant on chromosome 7 is strongly associated with susceptibility to sporadic amyotrophic lateral sclerosis (ALS). The genome-wide study, published online December 16 in Nature Genetics, identifies a variant of DPP6, a gene known to downregulate more than 50% after spinal cord injury in rats.
ALS, commonly known as Lou Gehrig's disease, is a progressive, debilitating, and always fatal neurological disorder that destroys motor neurons. Although 10% of ALS cases are familial and have been associated with mutations in several genes, the remaining 90% are sporadic. Earlier reports linking ALS susceptibility to genetic variants and copy number variations were frequently not supported by studies in other populations.
The new study is the first to identify a variant highly associated with ALS susceptibility across a large sample (1767 patients with ALS, 1916 patients without the condition), using independent populations from the Netherlands, United States, Sweden, and Belgium. The analysis found only 1 single nucleotide polymorphism (SNP) with genome-wide significance — an SNP in DPP6 (overall P = 5.04 × 10−8). ALS susceptibility was also higher for carriers with 2 copies of the risk allele (odds ratio [OR], 1.60; 95% confidence interval [CI] = 1.32 – 1.92) than for those with 1 copy (OR, 1.20; 95% CI = 1.06 – 1.41).
Identifying a common variant within DPP6 is "an exciting first step in the genetic study of sporadic ALS," concludes the report.
Coauthor Roel A. Ophoff, PhD, from the Department of Medical Genetics, University Medical Center, Utrecht, the Netherlands, and the Neuropsychiatric Institute, University of California, Los Angeles, discussed its significance in an email to Medscape Pathology: "Our finding is the first genetic association for sporadic ALS with convincing statistical evidence. That means that we have now for the first time an 'anchor point,' highlighting a pathway that is involved in the disease etiology."
However, Dr. Ophoff cautioned, "[T]hat doesn't mean that a treatment is at hand because we have 1 gene now.... There are many steps ahead."
Nat Genet. Published online December 16, 2007.