IGF1R rs907806 and GHSR rs572169 genetic variants in fetal macrosomia

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BACKGROUND: Being strongly affected by maternal and fetal genetic factors, intrauterine environment plays a critical role in fetal growth. Intrauterine conditions, in turn, are largely determined by the genetic factors.

AIM: The aim of this study was to evaluate the effect of the IGF1R rs907806 and GHSR rs572169 genetic variants on the weight of newborns.

MATERIALS AND METHODS: This prospective study included 221 mother-newborn pairs. The inclusion criteria were singleton pregnancy and informed consent to participate in the study. The exclusion criteria were severe somatic, oncological and acute illnesses three months prior or during pregnancy, gestational diabetes mellitus, refusal to participate in the study at any stage, and insufficient data. The study groups included patients with type 1 diabetes mellitus (group I), type 2 diabetes mellitus (group II), and no carbohydrate metabolism disorders (group III). Cord blood samples were obtained after delivery. The IGF1R rs907806 and GHSR rs572169 genotypes were determined by polymerase chain reaction with restriction fragment length polymorphism analysis. The main outcomes were delivery of a large for gestational age fetus (weight of more than the 90th percentile INTERGROWTH-21st). The secondary outcomes were diabetic fetopathy, diabetic cardiomyopathy, and neonatal hypoglycemia.

RESULTS: In group III, the minor G allele of the IGF1R rs907806 variant was more frequent in large-for-gestational-age newborns (p = 0.017; odds ratio 3.039; 95% confidence interval 1.244–7.424) than in those with a weight of less than 90th percentile. For the GHSR rs572169 variant, no similar trend was observed. This pattern was pronounced in the male newborns only (rs907806 AA vs. AG+GG; p = 0.046; odds ratio 4.229, 95% confidence interval 1.181–15.139). In newborns with hypoglycemia, a higher frequency of the GG genotype of the GHSR rs572169 (G>A) variant was observed in the total sample (p = 0.004) and the type 1 diabetes mellitus group (p = 0.0496).

CONCLUSIONS: The IGF1R rs907806 variant may affect birthweight in the male newborns of mothers without carbohydrate metabolism disorders. The observed association of neonatal hypoglycemia with the GG genotype of the GHSR rs572169 variant requires further investigation. Genetic factors can contribute to prognostic models of perinatal complications, while improving their early diagnosis opportunities.

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作者简介

Elena Alekseenkova

The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott

编辑信件的主要联系方式.
Email: ealekseva@gmail.com
ORCID iD: 0000-0002-0642-7924
SPIN 代码: 3976-2540
俄罗斯联邦, Saint Petersburg

Ziravard Tonyan

The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott

Email: ziravard@yandex.ru
ORCID iD: 0000-0001-9050-5886
SPIN 代码: 3787-7135
俄罗斯联邦, Saint Petersburg

Yulia Nasykhova

The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott

Email: yulnasa@gmail.com
ORCID iD: 0000-0002-3543-4963
SPIN 代码: 9661-9416

Cand. Sci. (Biol.)

俄罗斯联邦, Saint Petersburg

Ekaterina Kopteeva

The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott

Email: ekaterina_kopteeva@bk.ru
ORCID iD: 0000-0002-9328-8909
SPIN 代码: 9421-6407
俄罗斯联邦, Saint Petersburg

Roman Kapustin

The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott

Email: kapustin.roman@gmail.com
ORCID iD: 0000-0002-2783-3032
SPIN 代码: 7300-6260

MD, Dr. Sci. (Med.)

俄罗斯联邦, Saint Petersburg

Igor Kogan

The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott

Email: ikogan@mail.ru
ORCID iD: 0000-0002-7351-6900
SPIN 代码: 6572-6450

Dr. Sci. (Med.), Professor, Corresponding Member of the Russian Academy of Sciences

俄罗斯联邦, Saint Petersburg

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1. JATS XML
2. Appendix 1. Clinical characteristics of mothers and newborns.
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3. Appendix 2. Distribution of newborns by IGF1R rs907806 and GHSR rs572169 genetic variants.
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4. Appendix 3. Association of LGA with carriage of one or more minor alleles of the IGF1R rs907806 or GHSR rs572169 variants.
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5. Appendix 4. Distribution of LGA newborn girls by IGF1R rs907806 and GHSR rs572169 genetic variants.
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6. Appendix 5. Distribution of LGA newborn boys by IGF1R rs907806 and GHSR rs572169 genetic variants.
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7. Fig. 1. Study design. DM, diabetes mellitus; OGTT, oral glucose tolerance test

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8. Fig. 2. Birthweight Z-score distribution and the IGF1R rs907806 genotype. DM, diabetes mellitus

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9. Fig. 3. Birthweight Z-score distribution and the GHSR rs572169 genotype. DM, diabetes mellitus

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10. Fig. 4. Association of minor alleles of the IGF1R rs907806 and GHSR rs572169 polymorphism with fetal weight greater than the 90th percentile for gestational age. DM, diabetes mellitus

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СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
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