RESEARCH PAPER
Seeking genetic determinants of selected metabolic disorders in women aged 45–60
 
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1
Department of Nursing, Pomeranian Medical University, Szczecin, Poland
2
Primary Care Department, Pomeranian Medical University, Szczecin, Poland
3
Department of Clinical Nursing, Pomeranian Medical University, Szczecin, Poland
CORRESPONDING AUTHOR
Anna Jurczak   

Pomeranian Medical University in Szczecin, Department of Nursing, Poland
 
KEYWORDS
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ABSTRACT
Introduction and objective:
The biochemical and anthropometric consequences of metabolic disorders exert an enormous effect on the functioning of people worldwide. The aim of this study is to assess relationships between biochemical and anthropometric parameters associated with metabolic syndrome, and the presence of the PPAR-γ rs1801282, the FTO rs9939609, and the MC4R rs17782313 polymorphisms in women aged 45–60.

Material and methods:
The study included 425 women, aged 45–59 years, from the general population of the West Pomeranian Province in north-west Poland. The research procedure involved a structured interview, anthropometric and blood pressure measurements, biochemical analysis of serum, and genetic analysis.

Results:
The carriers of the A/A genotype of the FTO polymorphism had higher LDL levels than their counterparts with the T/T genotype (p = 0.01). The carriers of the T/T genotype of the MC4R polymorphism had lower non-HDL levels than those with the C/C and C/T genotypes (p = 0.019). Weight was related to the C/C and the C/G + G/G genotypes of the PPAR-γ gene polymorphism (p = 0.046). The model of inheritance for the MC4R polymorphism had a significant effect on TG (p = 0.039) and non-HDL (p = 0.05) levels.

Conclusions:
The genotypes analyzed in the study had only a slight direct effect on the biochemical and anthropometric abnormalities typical of metabolic disorders. Nonetheless, the risk alleles (A allele of the FTO rs9939609 and the C allele of the MC4R rs17782313) were found to be related to lipid metabolism disorders in 45–60-year-old women.

 
REFERENCES (32)
1.
Matsuo T, Nakata Y, Katayama Y, et al. PPARG genotype accounts for part of individual variation in body weight reduction in response to calorie restriction. Obesity (Silver Spring). 2009; 17(10): 1924–31. DOI: 10.1038/oby.2009.199.
 
2.
Bouchard C, Pérusse L. Current status of the human obesity gene map. Obes Res. 1996; 4: 81–90.
 
3.
Yen CJ, Beamer BA, Negri C, et al. Molecular scanning of the human peroxisome proliferator activated receptor gamma (hPPAR gamma) gene in diabetic Caucasians: identification of a Pro12Ala PPAR gamma 2 missense mutation. Biochem Biophys Res Commun. 1997; 241: 270–274. DOI: 10.1006/bbrc.1997.7798.
 
4.
Deeb SS, Fajas L, Nemoto M, et al. A Pro12Ala substitution in PPARgamma2 associated with decreased receptor activity, lower body mass index and improved insulin sensitivity. Nat Genet. 1998; 20: 284–287. DOI: 10.1038/3099.
 
5.
Cecil JE, Watt P, Palmer CN, et al. Energy balance and food intake: the role of PPARgamma gene polymorphisms. Physiol Behav. 2006; 88(3): 227–33. DOI: 10.1016/j.physbeh.2006.05.028.
 
6.
Rankinen T, Zuberi A, Chagnon YC, et al. The human obesity gene map: the 2005 update. Obesity (Silver Spring). 2006; 14: 529–644. DOI: 10.1038/oby.2006.71.
 
7.
Vogels N, Mariman EC, Bouwman FG, et al. Relation of weight maintenance and dietary restraint to peroxisome proliferator-activated receptor gamma2, glucocorticoid receptor, and ciliary neurotrophic factor polymorphisms. Am J Clin Nutr. 2005; 82: 740–746.
 
8.
Song Y, You NC, Hsu YH, et al. FTO polymorphisms are associated with obesity but not diabetes risk in postmenopausal women. Obesity (Silver Spring). 2008; 16(11): 2472–80. DOI: 10.1038/oby.2008.
 
9.
Phani NM, Vohra M, Rajesh S, et al. Implications of critical PPARγ2, ADIPOQ and FTO gene polymorphisms in type 2 diabetes and obesity-mediated susceptibility to type 2 diabetes in an Indian population. Mol Genet Genomics. 2016; 291(1): 193–204. DOI: 10.1007/s00438–015–1097–4.
 
10.
Frayling TM, Timpson NJ, Weedon MN, et al. A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science. 2007; 316: 889–894. DOI: 10.1126/science.1141634.
 
11.
Kang Y, Liu F, Liu Y. Is FTO gene variant related to cancer risk independently of adiposity? An updated meta-analysis of 129,467 cases and 290,633 controls. Oncotarget. 2017; 8(31): 50987–50996. DOI: 10.18632/oncotarget.16446.
 
12.
Mutombo PB, Yamasaki M, Hamano T, et al. MC4R rs17782313 gene polymorphism was associated with glycated hemoglobin independently of its effect on BMI in Japanese: the Shimane COHRE study. Endocr Res. 2014; 39(3): 115–9. DOI: 10.3109/07435800.2013.844163.
 
13.
Leońska-Duniec A, Jastrzębski Z, Zarębska A, et al. Impact of the Polymorphism Near MC4R (rs17782313) on Obesity- and Metabolic-Related Traits in Women Participating in an Aerobic Training Program. J Hum Kinet. 2017; 58: 111–119. DOI: 10.1515/hukin-2017–0073.
 
14.
Statistical Yearbook. Zachodniopomorskie Voivodship 2015. Statistical Office in Szczecin.
 
15.
Szkup M, Owczarek AJ, Schneider-Matyka D, Brodowski J, Łój B, Grochans E. The fat mass of the peroxisome proliferator-activated receptor gamma (PPAR-γ) and obesity-associated (FTO), and the melanocortin-4 receptor (MC4R) genes. Aging (Albany NY). 2018; 10(1): 72–82. DOI: 10.18632/aging.101360.
 
16.
Szkup M, Brodowski J, Owczarek AJ, Choręza P, Jurczak A, Grochans E. Searching for factors raising the incidence of metabolic syndrome among 45–60-year-old women. Aging Dis. 2018; 9(5): 831–842. DOI: 10.14336/AD.2017.1027.
 
17.
Alberti KG, Eckel RH, Grundy SM, et al. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation. 2009; 120(16): 1640–5.
 
18.
Miller S, Dykes D, Plesky H. A simple salting out procedure for extracting DNA from human nucleated cells. Nucl. Acids Res. 1988; 16: 1215. DOI: 10.1093/nar/16.3.1215.
 
19.
Dytfeld J, Horst-Sikorska W. Znaczenie receptorów aktywowanych proliferatorami peroksysomów γ (PPARγ) w fizjologii i patologii człowieka. [Peroxisomal proliferator-activated receptors γ (PPARγ) in human physiology and pathology]. Przegl Kardiodiabetol. 2009; 4: 187–191. In Polish.
 
20.
Cecil JE, Fischer B, Doney AS, et al. The Pro12Ala and C-681G variants of the PPARG locus are associated with opposing growth phenotypes in young schoolchildren. Diabetologia. 2005; 48: 1496–1502. DOI: 10.1007/s00125–005–1817–0.
 
21.
Cole SA, Mitchell BD, Hsueh WC, et al. The Pro12Ala variant of peroxisome proliferator-activated receptor-gamma2 (PPAR-gamma2) is associated with measures of obesity in Mexican Americans. Int J Obes Relat Metab Disord. 2000; 24(4): 522–4.
 
22.
Swarbrick MM, Chapman CM, McQuillan BM, et al. Pro12Ala polymorphism in the human peroxisome proliferator activated receptor gamma 2 associated with combined hyperlipidaemia in obesity. Eur J Endocrinol. 2001; 144: 277–282.
 
23.
Altshuler D, Hirschhorn JN, Klannemark M, et al. The common PPARgamma Pro12Ala polymorphism is associated with decreased risk of type 2 diabetes. Nat Genet. 2000; 26: 76–80. DOI: 10.1038/79216.
 
24.
Sanghera DK, Demirci FY, Been L, et al. PPARG and ADIPOQ gene polymorphisms increase type 2 diabetes mellitus risk in Asian Indian Sikhs: Pro12Ala still remains as the strongest predictor. Metabolism. 2010; 59(4): 492–501. DOI: 10.1016/j.metabol.2009.07.043.
 
25.
Qi Q, Kilpeläinen TO, Downer MK, et al. FTO genetic variants, dietary intake and body mass index: insights from 177 330 individuals. Hum Mol Genet. 2014; 23(25): 6961–6972. DOI: 10.1093/hmg/ddu411.
 
26.
Zeggini E, Weedon MN, Lindgren CM, et al. Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes. Science. 2007; 316: 1336–1341. DOI: 10.1126/science.1142364.
 
27.
Li H, Wu Y, Loos RJ, et al. Variants in FTO gene are not associated with obesity in a Chinese Han population. Diabetes. 2007; 57: 264–268. DOI: 10.2337/db07–1130.
 
28.
Ohashi J, Naka I, Kimura R, et al. FTO polymorphisms in oceanic populations. J Hum Genet 2007; 52: 1031–1035. DOI: 10.1007/s10038–007–0198–2.
 
29.
Binh TQ, Phuong PT, Nhung BT, et al. Association of the common FTO-rs9939609 polymorphism with type 2 diabetes, independent of obesity-related traits in a Vietnamese population. Gene. 2013; 513(1): 31–5. DOI: 10.1016/j.gene.2012.10.082.
 
30.
Wang T, Ma X, Peng D, et al. Effects of Obesity Related Genetic Variations on Visceral and Subcutaneous Fat Distribution in a Chinese Population. Sci Rep. 2016; 6: 20691. DOI: 10.1038/srep20691.
 
31.
Qi L, Kraft P, Hunter DJ, et al. The common obesity variant near MC4R gene is associated with higher intakes of total energy and dietary fat, weight change and diabetes risk in women. Hum Mol Genet. 2008; 17(22): 3502–3408. DOI: 10.1093/hmg/ddn242.
 
32.
Loos RJ, Lindgren CM, Li S, et al. Common variants near MC4R are associated with fat mass, weight and risk of obesity. Nat Genet. 2008; 40(6): 768–775. DOI: 10.1038/ng.140.
 
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