Genetic modifiers of nutritional status in cystic fibrosis
Genetic modifiers of nutritional status in cystic fibrosis
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DOI：
10.3945/ajcn.112.043406
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发表时间：
2012-12-01
影响因子：
7.1
通讯作者：
Cutting, Garry R.
中科院分区：
文献类型：
--
作者：
Bradley, Gia M.;Blackman, Scott M.;Cutting, Garry R.
背景：囊性纤维化（CF）患者早期营养改善与肺功能改善相关。然而，营养状况与CFTR genotype.Objective相关性很差：我们调查了修饰基因在多大程度上影响CF儿童的营养。设计图：BMI数据从CF双胞胎研究和囊性纤维化基金会患者登记处纵向收集，从2000年到2010年。通过计算5-10岁年龄段的平均BMI z评分（BMI-z（5 - 10）），得出1124例受试者的营养表型。通过比较同卵双生子与异卵双生子和同胞的表型相似性，估计对BMI-z（5 - 10）变异的遗传贡献（即遗传力）。结果：BMI-z（5 ~ 10）的中位数为-0.07（范围：-3.89 ~2.30），相当于CDC的第47百分位数。BMI-z（5 - 10）与胰腺功能不全、胎粪病史和女性呈负相关，但与晚出生队列和肺功能呈正相关。单卵双胞胎的BMI-z（5 - 10）一致性高于双卵双胞胎和兄弟姐妹;仅同性双胞胎分析的遗传力估计值范围为0.54 - 0.82。对于1010例胰腺功能不全受试者，在染色体1p36.1 [比值对数（LOD）：5.3]和5 q14（LOD：5.1）上确定了全基因组显著连锁。这些位点解释>= 16%和>= 15%，分别为BM 1 variation.Conclusions：双胞胎和兄弟姐妹CF的分析表明，一个突出的作用，基因以外的CFTR BMI的变化。具体来说，1号和5号染色体上的区域似乎含有具有实质性影响的遗传修饰剂。美国临床坚果杂志-2012;96：1299-308。
Background: Improved nutrition early in life is associated with better pulmonary function for patients with cystic fibrosis (CF). However, nutritional status is poorly correlated with the CFTR genotype.Objective: We investigated the extent to which modifier genes influence nutrition in children with CF. Design: BMI data were longitudinally collected from the CF Twin-Sibling Study and Cystic Fibrosis Foundation Patient Registry for twins and siblings from 2000 to 2010. A nutritional phenotype was derived for 1124 subjects by calculating the average BMI z score from 5-10 y of age (BMI-z(5to10)). The genetic contribution to the variation in BMI-z(5to10) (ie, heritability) was estimated by comparing the similarity of the phenotype in monozygous twins to that in dizy2ous twins and siblings. Linkage analysis identified potential modifier-gene loci.Results: The median BMI-z(5to10) was -0.07 (range: -3.89 to 2.30), which corresponded to the 47th CDC percentile. BMI-z(5to10) was negatively correlated with pancreatic insufficiency, history of meconium Hells, and female sex but positively correlated with later birth cohorts and lung function. Monozygous twins showed greater concordance for BMI-z(5to10) than did dizygous twins and siblings; heritability estimates from same-sex twin-only analyses ranged from 0.54 to 0.82. For 1010 subjects with pancreatic insufficiency, genome-wide significant linkage was identified on chromosomes 1p36.1 [log of odds (LOD): 5.3] and 5q14 (LOD: 5.1). These loci explained >= 16% and >= 15%, respectively, of the BM1 variance.Conclusions: The analysis of twins and siblings with CF indicates a prominent role for genes other than CFTR to BMI variation. Specifically, regions on chromosomes 1 and 5 appear to harbor genetic modifiers of substantial effect. Am J Clin Nutt- 2012;96:1299-308.