Human Molecular Genetics Advance Access originally published online on February 27, 2006
Human Molecular Genetics 2006 15(7):1237-1243; doi:10.1093/hmg/ddl039
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Positive association between POU1F1 and mental retardation in young females in the Chinese Han population
1Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 294 Taiyuan Road, Shanghai 200031, China, 2Bio-X Life Science Research Center, Shanghai Jiao Tong University, Hao Ran Building, 1954 Hua Shan Road, Shanghai 200030, China, 3Institute of Population and Health, Northwest University, Xi'an 710069, China, 4Shanghai Institute of Mental Health, 600 South Wan Ping Road, Shanghai 200030, China, 5Shanghai Key Lab of Children's Environmental Sciences, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, 1665 Kong Jiang Road, Shanghai 200092, China and 6Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 319 Yue Yang Road, Shanghai 200031, China
* To whom correspondence should be addressed. Tel: +86 2162822491; Fax: +86 2162822491; Email: helin{at}nhgg.org (L. He) or Tel: +86 2163858528; Email: xmshen{at}shsmu.edu.cn (X. Shen)
Received December 12, 2005; Accepted February 21, 2006
Genetic defects attributable to the genes involved in the hypothalamus–pituitary–thyroid (HPT) gland axis can cause abnormal thyroid hormone function and mental retardation (MR). Pit-1, encoded by the POU1F1 gene on human chromosome 3p11, is a pituitary-specific transcription factor responsible for the expression of several pituitary hormones. Thyrotropin is one of these hormones and is an important regulator in the HPT axis. One of the symptoms of patients with POU1F1 mutations is hypothyroidism and abnormalities of the nervous system early in the period after birth. We performed a case–control association study and a quantitative analysis of IQ to investigate the possible genetic contribution of POU1F1 in the Chinese Han population. Pairwise linkage disequilibrium (LD) analysis showed that rs300996, snp-7057 and rs300977 were in strong LD. There were significant differences of allele, genotype and haplotype frequencies of these three single nucleotide polymorphisms (SNPs) between cases and controls. When we conducted a breakdown comparison between cases and controls within different gender groups, no positive results in males were found. In females, however, we found significant differences between cases and controls in allele frequency distribution of rs300996 (P=0.0003), snp-7057 (P=0.0001) and rs300977 (P=0.0005) and in the distributions of common haplotypes combined by these SNPs (global P=0.0050). The P-value was 0.0301 for rs300996 and 0.0397 for the haplotype combination of rs300996–snp-7057–rs300977 in the analysis of the quantitative effects of the alleles and haplotypes on IQ in females. Our data suggest that POU1F1 may affect MR through a gender-specific mechanism.
The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors.