具有性别二态性的青少年特发性脊柱侧凸的多基因阈值模型：卡特效应。

Polygenic threshold model with sex dimorphism in adolescent idiopathic scoliosis: the Carter effect.

机构信息

Departments of Orthopaedic Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA.

出版信息

J Bone Joint Surg Am. 2012 Aug 15;94(16):1485-91. doi: 10.2106/JBJS.K.01450.

DOI:10.2106/JBJS.K.01450

PMID:22992817

Abstract

BACKGROUND

Adolescent idiopathic scoliosis occurs between two and ten times more frequently in females than in males. The exact cause of this sex discrepancy is unknown, but it may represent a difference in susceptibility to the deformity. If this difference is attributable to genetic factors, then males with adolescent idiopathic scoliosis would need to inherit a greater number of susceptibility genes compared with females to develop the deformity. Males would also be more likely to transmit the disease to their children and to have siblings with adolescent idiopathic scoliosis. Such a phenomenon is known as the Carter effect, and the presence of such an effect would support a multifactorial threshold model of inheritance.

METHODS

One hundred and forty multiplex families in which more than one individual was affected with adolescent idiopathic scoliosis were studied. These families contained 1616 individuals, including 474 individuals with adolescent idiopathic scoliosis and 1142 unaffected relatives. The rates of transmission from the 122 affected mothers and from the twenty-eight affected fathers were calculated, and the prevalence among siblings was determined in the nuclear families of affected individuals.

RESULTS

The prevalence of adolescent idiopathic scoliosis in these multiplex families was lowest in sons of affected mothers (36%, thirty-eight of 105) and highest in daughters of affected fathers (85%, twenty-two of twenty-six). Affected fathers transmitted adolescent idiopathic scoliosis to 80% (thirty-seven) of forty-six children, whereas affected mothers transmitted it to 56% (133) of 239 children (p < 0.001). Siblings of affected males also had a significantly higher prevalence of adolescent idiopathic scoliosis (55%, sixty-one of 110) compared with siblings of affected females (45%, 206 of 462) (p = 0.04).

CONCLUSIONS

This study demonstrates the presence of the Carter effect in adolescent idiopathic scoliosis. This pattern can be explained by polygenic inheritance of adolescent idiopathic scoliosis, with a greater genetic load required for males to be affected.

摘要

背景

青少年特发性脊柱侧凸在女性中的发病率比男性高 2 至 10 倍。这种性别差异的确切原因尚不清楚，但它可能代表了对畸形的易感性差异。如果这种差异归因于遗传因素，那么患有青少年特发性脊柱侧凸的男性与女性相比，需要遗传更多的易感基因才能发生这种畸形。男性也更有可能将这种疾病遗传给他们的孩子，并使他们的兄弟姐妹患有青少年特发性脊柱侧凸。这种现象被称为卡特效应，这种效应的存在支持多因素阈值遗传模型。

方法

研究了 140 个多基因家族，其中超过一个个体患有青少年特发性脊柱侧凸。这些家族包含 1616 个人，包括 474 名患有青少年特发性脊柱侧凸的个体和 1142 名未受影响的亲属。计算了 122 名受影响母亲和 28 名受影响父亲的传递率，并确定了受影响个体的核心家庭中兄弟姐妹的患病率。

结果

在这些多基因家族中，受影响母亲的儿子中青少年特发性脊柱侧凸的患病率最低（36%，105 人中 38 人），受影响父亲的女儿中患病率最高（85%，26 人中 22 人）。受影响的父亲将青少年特发性脊柱侧凸传递给 46 名儿童中的 80%（37 人），而受影响的母亲将其传递给 239 名儿童中的 56%（133 人）（p <0.001）。受影响男性的兄弟姐妹中，青少年特发性脊柱侧凸的患病率也明显高于受影响女性的兄弟姐妹（55%，110 人中 61 人）（45%，462 人中 206 人）（p=0.04）。