APOE and TGF- 1 genes are associated with obesity phenotypes

Long, Jirong; Liu, P. Y.; Liu, Y. J.; Lü, Yan; Xiong, Dong Hai; Elze, Leo; Recker, Robert R.; Deng, Hong‐Wen

doi:10.1136/jmg.40.12.918

Cited by 48 publications

(40 citation statements)

References 50 publications

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“…ApoE participates in the transport of cholesterol and other lipids by interacting with low-density lipoprotein receptors among various cells of the body (Mahley and Rall 2000). It has been reported that the ApoE genotype is associated with obesity (Long et al 2003) and increased cholesterol levels during menopause (Hak et al 2004), which were prevailing in females during the menopause periods (Stevenson et al 1993;Akahoshi et al 1996;Pavon de Paz et al 2006). In addition, some studies have reported that the ApoE genotype is associated with differential reproductive efficiency (Gerdes et al 1996;Corbo et al 2004), indicating a possible role of ApoE in human reproduction.…”

Section: Discussionmentioning

confidence: 99%

ApoE genotypes are associated with age at natural menopause in Chinese females

Meng

Wang

Liu

et al. 2011

AGE

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Ages at natural menarche and menopause are influenced by several genetic factors. This study aimed to investigate the possible relationship between the apolipoprotein E (ApoE) genotype and the age at menarche and natural menopause in Chinese females. In the current study, 398 (elderly group, aged 47-80 years) and 825 (young group, aged 15-25 years) Chinese females were enrolled under informed content. Ages at natural menarche and menopause were obtained by questionnaires. ApoE genotypes were identified by restriction fragment length polymorphism analysis. In the elderly group, the number of pregnancies and live births and breastfeeding were associated with the age at menopause (P=0.008, P=0.002, and P=0.

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Section: Discussionmentioning

confidence: 99%

ApoE genotypes are associated with age at natural menopause in Chinese females

Meng

Wang

Liu

et al. 2011

AGE

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“…TGFb is a critical regulator of development and maintenance of intestinal epithelium [Hauck et al, 2005]. Notably, polymorphic sites in the TGFb gene are associated with diabetes and obesity phenotypes, e.g., body composition, increased insulin, and glucose levels [Long et al, 2003;Rosmond et al, 2003]. Therefore, on the basis of possible functional interaction between TGFb, GATA factors and FABP2, it seems to be a promising approach to study effects of polymorphism combinations in these genes on traits of the metabolic syndrome.…”

Section: Discussionmentioning

confidence: 99%

Type 2 diabetes-associated fatty acid binding protein 2 promoter haplotypes are differentially regulated by GATA factors

et al. 2007

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The human intestinal fatty acid binding protein 2 (FABP2) mediates fat absorption by binding and intracellular trafficking of long-chain free fatty acids. Studies with knockout mice and association analysis of polymorphisms revealed that FABP2 is a susceptibility gene for type 2 diabetes (noninsulin dependent diabetes mellitus [NIDDM]) and related traits. Relevant FABP2 promoter polymorphisms c.-80_-79insT (rs5861422), c.-136_-132delAGTAG (rs5861423), c.-168_-166delAAGinsT (rs1973598), c.-260G>A (rs6857641), c.-471G>A (rs2282688), and c.-778G>T (rs10034579) result in two haplotypes A and B, whereby B possesses two- to three-fold lower transcriptional activity than A. We show in luciferase reporter gene assays by a series of chimeric FABP2 promoter constructs in intestinal Caco-2 cells that polymorphism c.-80_-79insT essentially determines different activities of the FABP2 promoter. In accordance, in electrophoretic mobility shift assays (EMSAs), transcriptional factors GATA-5 and -6 bind with higher binding affinities to the FABP2 promoter region containing the -80A allele compared to B. As functional consequence, haplotype A is twice as much more activated by GATA factors than haplotype B in liver Huh7 cells. Additionally, a construct bearing the -80B allele in the background of haplotype A reversed the activity from A to B. Thus, the GATA mediated differential activation of FABP2 haplotypes depends on polymorphism c.-80_-79insT. This provides the molecular basis for the variant specific transcriptional regulation of the diabetes type 2-associated FABP2 gene.

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“…Several studies showed that population substructure may not be a problem for association studies in US Caucasian populations, 32 including our recent data for our study population. 33 The study subjects were recruited from a population of relatively homogenous ethnic background and population stratification was not observed. 33 Therefore, the results obtained in the present study should be robust and reliable.…”

Section: Statistical Issues Involved In Analyses and Their Implicationsmentioning

confidence: 99%

Common variants at the PCOL2 and Sp1 binding sites of the COL1A1 gene and their interactive effect influence bone mineral density in Caucasians

Liu

Lü

Long

et al. 2004

Journal of Medical Genetics

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Background: Osteoporosis, mainly characterised by low bone mineral density (BMD), is a serious public health problem. The collagen type I alpha 1 (COL1A1) gene is a prominent candidate gene for osteoporosis. Here, we examined whether genetic variants at the COL1A1 gene can influence BMD variation. Methods: BMD was measured at nine skeletal sites in 313 Caucasian males and 308 Caucasian females. We screened four single nucleotide polymorphisms (SNPs) at the COL1A1 gene: PCOL2 (-1997 G/T) in the promoter, Sp1 (1546 G/T) in the intron 1, Gly19Cys (3911 G/A) in exon 8, and Ala897Thr (13 773 G/A) in exon 45. Univariate and multivariate association approaches were used in the analyses. Results: In multivariate analyses, we found a strong association between the PCOL2 SNP and BMD (p = 0.007 to 0.024) and a suggestive association between the Sp1 SNP and BMD (p = 0.023 to 0.048) in elderly Caucasian females. Interestingly, the interaction of these two SNPs was highly significantly associated with BMD variation (p = 0.001 to 0.003). The haplotype GG at the two SNPs had, on average, 2.7% higher BMD than non-carriers (p = 0.006 to 0.026). Conclusions: Our data suggested that the common genetic variants at the PCOL2 and Sp1 sites, and importantly, their interactive effects, may contribute to BMD variation in elderly Caucasian females. Further studies are necessary to delineate the mechanisms underlying the effects of these common variants on BMD variation and to test their clinical relevance for general populations. In addition, our study highlighted the importance of multivariate analyses when multiple correlated phenotypes are under study.

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APOE and TGF- 1 genes are associated with obesity phenotypes

Cited by 48 publications

References 50 publications

ApoE genotypes are associated with age at natural menopause in Chinese females

ApoE genotypes are associated with age at natural menopause in Chinese females

Type 2 diabetes-associated fatty acid binding protein 2 promoter haplotypes are differentially regulated by GATA factors

Common variants at the PCOL2 and Sp1 binding sites of the COL1A1 gene and their interactive effect influence bone mineral density in Caucasians

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