Abstract
Objectives: Because of their location in known candidate gene regions for obesity the associations between six microsatellite markers (D2S2170, D2S144, D2S1268, D2S1788, D2S1348 and a tetranucleotide repeat in the 3′ UTR of the LEP locus) and body mass index (BMI) were studied in adult Samoans.
Design: The study was designed to detect differences in the proportion of alleles at the six microsatellite markers between two groups of adult Samoans at the extremes of the longitudinal BMI distribution.
Subjects and Measurements: The 181 unrelated Samoan participants were 25–55 y of age, reported that all four grandparents were Samoan, resided in American Samoa (AS) or Samoa (S) and were without diagnosed hypertension or type 2 diabetes. Initial statistical analysis was based on χ2 tests of independence between marker allele frequencies and BMI status at each marker. The association of individual alleles with BMI status was tested by aggregating a marker's allelic data into a two-by-two contingency table and applying a two-tailed version of Fisher's exact test, with a Bonferroni correction to account for the multiple testing implicit in the procedure.
Results: There were no significant differences in allele frequencies at any of the markers between AS and S, as expected from our prior population genetic analyses. Only the LEP gene 3′-tetranucelotide repeat was associated (P<0.006) with BMI status. The distribution of the marker alleles at the LEP locus was significantly associated with the BMI groups (P<0.01), due to the low frequency of allele 226 in the high BMI group. The same pattern of association was found in sub-group analyses with low BMI individuals from AS and high BMI individuals from S.
Conclusion: These findings indicate that the leptin 3′-tetranucleotide repeat is associated with high BMI in adult Samoans, with allele 226 having a low frequency in the high BMI group.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Perusse L, Chagnon YC, Weisnagel SJ, Rankinen T, Snyder E, Sands J, Bouchard C . The human obesity gene map: the 2000 update Obes Res 2001 9: 135–169.
McGinnis JM, Foege WH . Actual causes of death in the United States JAMA 1993 270: 2207–2212.
Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM . Positional cloning of the mouse obese gene and its human homologue Nature 1994 372: 425–432.
Borecki IB, Rice T, Perusse L, Bouchard C, Rao DC . An exploratory investigation of genetic linkage with body composition and fatness phenotypes: the Quebec family study Obes Res 1994 2: 213–219.
Clement K, Garner C, Hager J, Philippi A, LeDuc C, Carey A, Harris TJ, Jury C, Cardon LR, Basdevant A, Demenais F, Guy-Grand B, North M, Froguel P . Indication for linkage of the human OB gene region with extreme obesity Diabetes 1996 45: 687–690.
Duggirala R, Stern MP, Mitchell BD, Reinhart LJ, Shipman PA, Uresandi OC, Chung WK, Leibel RL, Hales CN, O'Connell P, Blangero J . Quantitative variation in obesity-related traits and insulin precursors linked to the OB gene region on human chromosome 7 Am J Hum Genet 1996 59: 694–703.
Norman RA, Leibel RL, Chung WK, Power-Kehoe L, Chua SC Jr Knowler WC, Thompson DB, Bogardus C, Ravussin E . Absence of linkage of obesity and energy metabolism to markers flanking homologues of rodent obesity genes in Pima Indians Diabetes 1996 45: 1229–1232.
Reed DR, Ding Y, Xu W, Cather C, Green ED, Price RA . Extreme obesity may be linked to markers flanking the human OB gene Diabetes 1996 45: 691–694.
Bray MS, Boerwinkle E, Hanis CL . OB gene not linked to human obesity in Mexican American affected sib pairs from Starr County, Texas Hum Genet 1996 98: 590–595.
Shintani M, Ikegami H, Yamato E, Kawaguchi Y, Fujisawa T, Nakagawa Y, Hamada Y, Ueda H, Miki T, Ogihara T . A novel microsatellite polymorphism in the human OB gene: a highly polymorphic marker for linkage analysis Diabetologia 1996 39: 1398–1401.
Hasstedt SJ, Hoffman M, Leppert MF, Elbein SC . Recessive inheritance of obesity in familial non-insulin-dependent diabetes mellitus, and lack of linkage to nine candidate genes Am J Hum Genet 1997 61: 668–677.
Oksanen L, Ohman M, Heiman M, Kainulainen K, Kaprio J, Mustajoki P, Koivisto V, Koskenvuo M, Janne OA, Peltonen L, Kontula K . Markers for the gene ob and serum leptin levels in human morbid obesity Hum Genet 1997 99: 559–564.
DeSilva U, Massa H, Trask BJ, Green ED . Comparative mapping of the region of human chromosome 7 deleted in williams syndrome Genome Res 1999 9: 428–436.
Allison DB, Heo M . Meta-analysis of linkage data under worst-case conditions: a demonstration using the human OB region Genetics 1998 148: 859–865.
McGarvey ST, Baker PT . The effects of modernization and migration on Samoan blood pressure Hum Biol 1979 51: 461–479.
Bindon JR, Baker PT . Modernization, migration & obesity among Samoan adults Ann Hum Biol 1985 12: 67–76.
McGarvey ST . Obesity in Samoans and a perspective on its etiology in Polynesians Am J Clin Nutr 1991 53: 1586S–1594S.
McGarvey ST . The thrifty gene concept and adiposity studies in biological anthropology J Polynes Soc 1994 103: 29–42.
Gershater E, McGarvey ST . Fourteen year changes in adiposity and blood pressure in Samoan adults Am J Hum Biol 1995 7: 597–606.
Hodge AM, Dowse GK, Toelupe P, Collins VR, Imo T, Zimmet PZ . Dramatic increases in the prevalence of obesity in (Western) Samoa over the 13 y period 1978–1991 Int J Obes Relat Metab Disord 1994 18: 419–428.
Galanis DJ, McGarvey ST, Quested C, Sio B, Afele-Fa'amuli S . Dietary intake among modernizing Samoans: implications for risk of cardiovascular disease J Am Diet Assoc 1999 99: 184–190.
Hill AVS, Serjeantson SW . The colonization of the Pacific: a genetic trail Oxford University Press: London 1989.
Deka R, McGarvey ST, Ferrell RE, Kamboh MI, Yu LM, Aston CE, Jin L, Chakraborty R . Genetic characterization of American and Western Samoans Hum Biol 1994 66: 805–822.
Redd A, Takexaki N, Sherry S, McGarvey ST, Sofro ASM, Stoneking M . Evolutionary history of the COII/tRNALys intergenic 9 b.p. deletion in human mitochondrial DNAs from the Pacific Mol Biol Evol 1995 12: 604–615.
Parra E, Saha N, Soemantri AG, McGarvey ST, Hundrieser J, Shriver MD, Deka R . Genetic variation at 9 autosomal microsatellite loci in Asian and Pacific populations Hum Biol 1999 71: 757–779.
Neel JV . Diabetes mellitus: a ‘thrifty’ genotype rendered detrimental by ‘progress’? Am J Hum Genet 1962 14: 353–362.
Prior IAM . Nutritional problems in Pacific Islanders The 1976 Muriel Bell Memorial Lecture. Wellington. Nutrition Society of New Zealand: Wellington 1977.
Zimmet PZ . Epidemiology of diabetes and its macrovascular manifestations in Pacific populations: the medical effects of social progress Diabetes Care 1979 2: 144–153.
Baker PT . Migration, genetics and the degenerative diseases of South Pacific Islanders In: A Boyce (ed) Migration and mobility Taylor & Francis: London 1984 165–180.
Mountjoy KG, Wong J . Obesity, diabetes and functions for proopiomelanocortin-derived peptides Mol Cell Endocrinol 1997 128: 171–177.
Krude H, Grüters A . Implications of proopiomelanocortin (POMC) mutations in humans: the POMC deficiency syndrome Trends Endocrinol Metab 2000 11: 15–22.
Krude H, Biebermann H, Luck W, Horn R, Brabant G, Grüters A . Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans Nature Genet 1998 19: 155–157.
Delplanque J, Barat-Hourari M, Dina C, Gallina P, Clément K, Guy-Grand B, Vasseur F, Boutin P, Froguel P . Linkage and association studies between the proopiomelanocortin (POMC) gene and obesity in Caucasian families Diabetologia 2000 43: 1554–1557.
Hinney A, Becker I, Heibült O, Nottebom K, Schmidt A, Ziegler A, Mayer H, Siegfried W, Blum WF, Remschmidt H, Hebebrand J . J Clin Endocrinol Metab 1998 83: 3737–3741.
Commuzie AG, Hixson JE, Almasy L, Mitchell BD, Mahaney MC, Dyer TD, Stern MP, MacCluer JW, Blangero J . A major quantitative trait locus determining serum leptin levels and fat mass is located on human chromosome 2 Nature Genet 1997 15: 273–276.
Hixson JE, Almasy L, Cole S, Birnbaum S, Mitchell BD, Mahaney MC, Stern P, MacCluer JW, Blangero J, Commuzie AG . Normal variation in leptin levels is associated with polymorphisms in the proopiomelanocortin gene, POMC J Clin Endocrinol Metab 1999 84: 3187–3191.
US Dept of Commerce. Census of Population and Housing, American Samoa 1990 Washington, DC 1992.
Western Samoa Department of Statistics. Western Samoa Census 1991 Government Printing House: Apia 1995.
McGarvey ST, Levinson PD, Bausserman L, Galanis DJ, Hornick C . Population change in adult obesity and blood lipids in American Samoa from 1976–78 to 1990 Am J Hum Biol 1993 5: 17–30.
Chin-Hong PV, McGarvey ST . Lifestyle incongruity and adult blood pressure in Western Samoa Psychosom Med 1996 58: 130–137.
Agresti A . An introduction to categorical data analysis John Wiley: New York 1996.
Clarkson DB, Fan Y, Joe H . A remark on algorithm 643: FEXACT: an algorithm for performing Fisher's exact test in r×c contingency tables ACM Trans Math Software 1993 19: 484–488.
Freedman D, Pisani R, Purves R, Adhikari A . Statistics WW Norton: New York 1991.
de Silva AM, Walder KR, Aitman TJ, Gotoda T, Goldstone AP, Hodge AM, de Courten MP, Zimmet PZ, Collier GR . Combination of polymorphisms in OB-R and the OB gene associated with insulin resistance in Nauruan males Int J Obes Relat Metab Disord 1999 23: 816–822.
Hager J, Clement K, Francke S, Dina C, Raison J, Lahlou N, Rich N, Pelloux V, Basdevant A, Guy-Grand B, North M, Froguel P . A polymorphism in the 5′ untranslated region of the human ob gene is associated with low leptin levels Int J Obes Relat Metab Disord 1998 22: 200–205.
Li WD, Reed DR, Lee JH, Xu W, Kilker RL, Sodom BR, Price RA . Sequence variants in the 5′ flanking region of the leptin gene are associated with obesity in women Ann Hum Genet 1999 63: 227–234.
Mammes O, Betoulle D, Aubert R, Giraud V, Tuzet S, Petiet A, Colas-Linhart N, Fumeron F . Novel polymorphisms in the 5′ region of the LEP gene: association with leptin levels and response to low-calorie diet in human obesity Diabetes 1998 47: 487–489.
Considine RV, Sinha MK, Heiman ML, Kriauciunis A, Stephens TW, Nyce MR, Phannesian JP, Marco CC, McKee LJ, Bauer T, Caro JF . Serum immunoreactive-leptin concentrations in normal-weight and obese humans New Engl J Med 1996 334: 292–295.
Maffei M, Halaas JER, Pratley RE, Lee GH, Zhang Y, Fei H, Kim S, Lallone R, Ranganathan S, Kern PA, Friedman JM . Leptin levels in human and rodent: measurement of plasma leptin and RNA in obese and weight-reduced subjects Nature Med 1995 1: 1155–1161.
Acknowledgements
This research was supported by NIH grants AG09375, HL52611, DK55406, DK59642 and ES06096. We thank the members of the Department of Health, Government of Samoa, and the American Samoan Department of Health for their assistance in data collection, local political officials for their cooperation and the participants for their patience.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
McGarvey, S., Forrest, W., Weeks, D. et al. Human leptin locus (LEP) alleles and BMI in Samoans. Int J Obes 26, 783–788 (2002). https://doi.org/10.1038/sj.ijo.0801996
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.ijo.0801996
Keywords
This article is cited by
-
The association of insertions/deletions (INDELs) and variable number tandem repeats (VNTRs) with obesity and its related traits and complications
Journal of Physiological Anthropology (2017)
-
Genetic association study of selected candidate genes (ApoB, LPL, Leptin) and telomere length in obese and hypertensive individuals
BMC Medical Genetics (2009)
-
Obesity and polymorphisms in genes regulating human adipose tissue
International Journal of Obesity (2007)