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Absence of association between SNPs in the promoter region of the insulin-like growth factor 1 (IGF-1) gene and longevity in the Han Chinese population

Liang Xie a,b,c,1, Yuan-ying Gong a,c,1, Shi-gang Lian d, Juan Yang d, Ya Yang e, Shou-jun Gao f, Liang-you Xu f, Ya-ping Zhang a,b, *

aState Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China bLaboratory for Conservation and Utilization of Bio-Resource, Yunnan University, Kunming 650091, China cGraduate School of the Chinese Academy of Sciences, Beijing 100049, China dPeople’s Hospital of Dujiangyan City, Dujiangyan 611830, China eKey Laboratory of Animal Models and Human Disease Mechanisms and Learning and Memory, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, fDujiangyan Longevity Research Centre, Dujiangyan 611830, China

eKey Laboratory of Animal Models and Human Disease Mechanisms and Learning and Memory, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China fDujiangyan Longevity Research Centre, Dujiangyan 611830, China

Previous studies have indicated that genetic variations in the factors of insulin/insulin-like growth factor 1 (IGF-1) signaling pathway could influence human life-span by affecting IGF-1 levels. The promoter region of the IGF-1 gene is an obvious candidate and has not been studied clearly. To explore the potential role of the promoter region variation of IGF-1 gene in longevity, we investigated 485 longevity subjects and 392 younger individuals from Dujiangyan, China. By sequencing about 2.5 kb (kilo base pairs) upstream the transcription start site of exon 1 of the IGF-1 gene in 30 individuals from both groups respectively, we acquired three previously described SNPs ((cid:2)439T/A (rs2288377), (cid:2)541T/C (rs5742612) and (cid:2)1246C/T (rs35767)). We examined the association between these three SNPs and lon- gevity by comparing the distribution of genotypes, alleles, and haplotypes in both the longevity and con- trol groups. None of these variants were found to be associated with longevity. Our results suggest that there is no association between SNPs in the promoter region of IGF-1 gene and longevity in the Han Chi- nese population.

 2008 Elsevier Inc. All rights reserved.

1. Introduction

tors in this pathway may contribute to longevity by affecting IGF-1 level. Furthermore, Bonafe et al. suggested that 3173A/G (rs2229765) in the IGF-1 receptor (IGF-1R) is associated with the production of IGF-1 (Bonafe et al., 2003). Another study reported that (cid:2)202A/C (rs2854744) located in insulin-like growth factor binding protein 3 (IGFBP3) promoter region could affect the circu- lating level of IGFBP3, which might influence circulating levels of IGF-1 accordingly (Deal et al., 2001). Recently, one study in cente- narians suggested that variations of IGF-1R may contribute to lon- gevity gender-specifically by increasing the IGF-1 levels in female centenarians (Suh et al., 2008). Meanwhile, another study sup- ported that the specific SNPs in IGF-1 gene can influence circulat- ing level of IGF-1 significantly (Patel et al., 2008). Unfortunately, as far as we know, there is still no research on the association be- tween the polymorphisms of the IGF-1 promoter region and lon- gevity, although the promoter region is important to the expression of the IGF-1 gene and serum IGF-1 levels. To explore the potential role of the promoter region variation of the IGF-1 gene in longevity, we performed an association study on the SNPs of the promoter region of IGF-1 and longevity in the Han Chinese population.

Ageing is a complex physical process with a variety of changes occurring in many aspects of bodily functions such as physiology and endocrinology. In this process, genetic and environmental fac- tors interact with each other and greatly contribute to the aging process. In 2001, Mitchell et al. estimated a heritability of 25% of the life-span in an Amish population in Lancaster County, Pennsyl- vania (Mitchell et al., 2001), which implied a relatively strong ge- netic background in human life-span. Meanwhile, in invertebrate (Kenyon, 2001) and mice (Holzenberger et al., 2003) studies, a con- served insulin/IGF-1 signaling pathway was speculated to be in- volved in the regulation of longevity (Bartke, 2008; Tatar et al., 2003). IGF-1 is one of the major factors in the Insulin/IGF-1 signal- ing pathway. In humans, several studies suggested that an optimal level of circulating IGF-1 was beneficial for longevity (Juul, 2003;

* Corresponding author. Address: State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China. Tel.: +86 871 519 9030; fax: +86 871 519 5430.

E-mail addresses: zhangyp@mail.kiz.ac.cn, zhangyp1@263.net.cn (Y.-p. Zhang). 1 These authors have equal contributions to this paper.

0531-5565/$ - see front matter r © z 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.exger.2008.08.004

2. Materials and methods

2005), respectively. The haplotype estimation was conducted Phase 2.1 software (Stephens and Scheet, 2005; Stephens et 2001). Statistical analyses were performed by SPSS software age (SPSS version 13.0, Chicago, IL). The genotype and frequencies in both groups were compared by Pearson’s chi test. The p value is two tailed and the cut off value was 0.05. SNP alleles, we calculated three categories of p values for the ent probable function of the mutant allele as follows: inhibitive, and codominant, which was identical to a study (Canzian et al., 2006).

2.1. Subjects